[go: up one dir, main page]

US20030185761A1 - Buccal, polar and non-polar spray or capsule containing drugs for treating pain - Google Patents

Buccal, polar and non-polar spray or capsule containing drugs for treating pain Download PDF

Info

Publication number
US20030185761A1
US20030185761A1 US10/230,059 US23005902A US2003185761A1 US 20030185761 A1 US20030185761 A1 US 20030185761A1 US 23005902 A US23005902 A US 23005902A US 2003185761 A1 US2003185761 A1 US 2003185761A1
Authority
US
United States
Prior art keywords
composition
amount
active compound
percent
weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/230,059
Inventor
Harry Dugger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Flemington Pharmaceutical Corp
Original Assignee
Flemington Pharmaceutical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US1997/017899 external-priority patent/WO1999016417A1/en
Application filed by Flemington Pharmaceutical Corp filed Critical Flemington Pharmaceutical Corp
Priority to US10/230,059 priority Critical patent/US20030185761A1/en
Assigned to NOVADEL PHARMA INC. reassignment NOVADEL PHARMA INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DUGGER, HARRY A., III
Priority to PCT/US2003/026859 priority patent/WO2004043428A2/en
Priority to JP2004551444A priority patent/JP2006505611A/en
Priority to NZ539284A priority patent/NZ539284A/en
Priority to AU2003296899A priority patent/AU2003296899A1/en
Priority to CA002497268A priority patent/CA2497268A1/en
Priority to EP03811212A priority patent/EP1539107A2/en
Priority to US10/671,710 priority patent/US20040136913A1/en
Publication of US20030185761A1 publication Critical patent/US20030185761A1/en
Priority to US10/726,625 priority patent/US6969508B2/en
Priority to US11/366,663 priority patent/US20060165604A1/en
Assigned to PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT FOR SECURED PARTIES reassignment PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT FOR SECURED PARTIES SECURITY AGREEMENT Assignors: NOVADEL PHARMA INC.
Priority to US12/351,606 priority patent/US20090124554A1/en
Priority to US12/351,576 priority patent/US20090162298A1/en
Assigned to NOVADEL PHARMA INC. reassignment NOVADEL PHARMA INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT
Priority to US13/467,441 priority patent/US20120252846A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. Pat. No. 3,155,574, Silson et al., U.S. Pat. No. 5,011,678, Wang et al., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered.
  • a buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect.
  • the composition comprises: propellant 10-70%, non-polar solvent 25-89.9%, active compound 0.01-40%, flavoring agent 1-8%; most suitably propellant 20-70%, non-polar solvent 25-74.75%, active compound 0.25-35%, flavoring agent 2-7.5%.
  • compositions of the present invention for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent are also administrable in aerosol form driven by a propellant.
  • the composition comprises in weight % of total composition: aqueous polar solvent 10-97%, active compound 0.1-25%, suitably additionally comprising, by weight of total composition a flavoring agent 0.05-10% and propellant: 2-10%.
  • the composition comprises: polar solvent 20-97%, active compound 0.1-15%, flavoring agent 0.1-5% and propellant 2-5%; most suitably polar solvent 25-97%, active compound 0.2-25%, flavoring agent 0.1-2.5% and propellant 2-4%.
  • the buccal pump spray composition of the present invention i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound wherein said active compound is soluble in a pharmacologically acceptable non-polar solvent comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, and suitably additionally, flavoring agent 0.1-10%.
  • the composition comprises: polar solvent 37-98.58%, active compound 0.005-55%, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01-40%, flavoring agent 0.75-7.5%.
  • the soft bite gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable non-polar solvent, having charged thereto a fill composition comprise in weight % of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01-80%, provided that said fill composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 0.01-10%.
  • the soft bite gelatin capsule comprises: non-polar solvent 21.5-99.975%, emulsifier 0-15%, active compound 0.025-70%, flavoring agent 1-8%; most suitably: nonpolar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1-65.0%, flavoring agent 2-6%.
  • the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0-15%, active compound 0.025-55%, flavoring agent 1-8%; most suitably: polar solvent 44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%.
  • a further object is a sealed aerosol spray container containing a composition of the non polar or polar aerosol spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
  • the propellant is a non-Freon material, preferably a C 3-8 hydrocarbon of a linear or branched configuration.
  • the propellant should be substantially non-aqueous.
  • the propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.
  • the non-polar solvent is a non-polar hydrocarbon, preferably a C 7-18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol.
  • the solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at a temperature of 0-40° C. a pressure range of between 1-3 atm.
  • the polar and non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, which does not allow entry of atmospheric gasses with each activation.
  • a metered valve which does not allow entry of atmospheric gasses with each activation.
  • a further object is a pump spray container containing a composition of the pump spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
  • a further object is a soft gelatin bite capsule containing a composition of as set forth above.
  • the formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.)
  • the polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound.
  • the solvent preferably dissolves the active compound.
  • other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill.
  • Soft gelatin capsules are well known in the art. See, for example, U.S. Pat. No. 4,935,243, Borkan et al., for its teaching of such capsules.
  • the capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds.
  • the shell of a soft gelatin capsule of the invention may comprise, for example: gelatin: 50-75%, glycerin 20-30%, colorants 0.5-1.5%, water 5-10%, and sorbitol 2-10%.
  • the active compound may include, biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals.
  • the active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application.
  • the active compounds may also include nerve impulse inhibitors, anti-opioid agents, anti-migraine agents, anti-muscle spasm agents, pain control agents, anesthetics, anti-inflammatory drugs, or mixtures thereof.
  • FIG. 1. is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.
  • the preferred active compounds of the present invention are in an ionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or pump spray compositions, they are soluble in the spray solvent). These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) first pass effect.
  • propellants for the non polar sprays propane, N-butane, iso-butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used.
  • N-butane and iso-butane, as single gases, are the preferred propellants. It is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1-0.2%. All percentages herein are by weight unless otherwise indicated. It is also preferable that the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The concentration of each of these should be less than 0.1%, except that water may be as high as 0.2%.
  • Suitable non-polar solvents for the capsules and the non-polar sprays include (C 2 -C 24 ) fatty acid (C 2 -C 6 ) esters, C 7 -C 18 hydrocarbon, C 2 -C 6 alkanoyl esters, and the triglycerides of the corresponding acids.
  • other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.
  • solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C 2 -C 8 ) mono and polyols and alcohols of C 7 -C 18 linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • PEG polyethyleneglycols
  • C 2 -C 8 low molecular weight mono and polyols and alcohols of C 7 -C 18 linear or branch chain hydrocarbons
  • glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • the preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc.), and combinations thereof.
  • the active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, octreotide acetate, calcitonin-salmon, insulin lispro, sumatriptan succinate, clozepine, cyclobenzaprine, dexfenfluramine hydrochloride, glyburide, zidovudine, erythromycin, ciprofloxacin, ondansetron hydrochloride, dimenhydrinate, cimetidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thromethamine, carboprost, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate and neutraceuticals, that is to say nutrients with pharmacological action such as but not limited to carnitine
  • the active compound is a nerve impulse inhibitor, anti-opioid agent, anti-migraine agent, anti-muscle spasm agent, pain control agent, anesthetic, anti-inflammatory drug, or a mixture thereof.
  • the active compound is a nerve impulse inhibitor.
  • Suitable nerve impulse inhibitors for use in the buccal sprays of the invention include, but are not limited to levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxacurium, mivacurium, pancuronium, vecuronium, pipecuronium, rocuronium, and mixtures thereof.
  • the active compound is an anti-opioid agent.
  • Suitable anti-opioid agents for use in the buccal sprays of the invention include, but are not limited to, naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
  • the active compound is an anti-migraine agent.
  • Suitable anti-migraine agents for use in the buccal sprays of the invention include, but are not limited to, frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
  • the active compound is an anti-muscle spasm agent.
  • Suitable anti-muscle spasm agents for use in the buccal sprays of the invention include, but are not limited to, baclofen, botulinum toxin, carisoprodol, chlorphenesin, chlorzoxazone, cyclobenzaprine, dantrolene, diazepam, metaxalone, methocarbamol, orphenadrine, tizanidine, and mixtures thereof.
  • the active compound is a pain control agent.
  • Suitable pain control agents for use in the buccal sprays of the invention include, but are not limited to, non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
  • the active compound is an anesthetic.
  • Suitable anesthetics for use in the buccal sprays of the invention include, but are not limited to, benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
  • the active compound is an anti-inflammatory drug.
  • Suitable anti-inflammatory drugs for use in the buccal sprays of the invention include, but are not limited to, alosetron, anakinra, beclomethasone, betamethasone, budesonide, clobetasol, celecoxib, cromolyn, desoximetasone, dexamethasone, epinastic, etanercept, etoricoxib, flunisolide, fluocinonide, fluticasone, formoterol, hydrocortisone, hydroxychloroquine, ibudilast, ketotifen, meloxicam, mesalamine, methotrexate, methylprednisolone, mometasone, montelukast, nedocromil, olsalazine, prednisone, ramatroban, rofecoxib, salsalate, terbutaline, triamcino
  • compositions of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof.
  • pharmaceutically acceptable salts refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases.
  • salts may be prepared from pharmaceutically acceptable non-toxic bases.
  • Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts.
  • Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins such as arginine, betaine, caffeine, choline, N,N dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl-aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl-glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc.
  • basic ion-exchange resins such as arginine, betaine, caffeine, choline
  • salts may be prepared from pharmaceutically acceptable non-toxic acids.
  • acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane-sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc.
  • Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids.
  • Cyclosporine Lingual Spray preferred most preferred Amounts amount amount amount cyclosporine 5-50 10-35 15-25 water 5-20 7.5-50 9.5-12 ethanol 5-60 7.5-50 10-20 polyethylene glycol 20-60 30-45 35-40 flavors 0.1-5 1-4 2-3
  • Cyclosporine Non-Polar Lingual Spray preferred most preferred Amounts amount amount amount cyclosporine 1-50 3-40 5-30 Migylol 20 25 30-40 Polyoxyethylated castor oil 20 25 30-40 Butane 25-80 30-70 33-50 flavors 0.1-5 1-4 2-3
  • Cyclosporine Non-polar Bite Caosule preferred most preferred Amounts amount amount cyclosporine 1-35 5-25 10-20 olive oil 25-60 35-55 30-45 polyoxyethylated 25-60 35-55 30-45 oleic glycerides flavors 0.1-5 1-4 2-3
  • CNS Active Amines and their Salts Including but not Limited to Tricyclic Amines, GABA Analogues, Thiazides, Phenothiazine Derivatives, Serotonin Antagonists and Serotonin Reuptake Inhibitors
  • Clozepine Lingual Spray preferred most preferred Amounts amount amount amount clozepine 0.5-30 1-20 10-15 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-15 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 10-15 flavors 0.1-5 1-4 2-3
  • Glyburide Lingual Spray preferred most preferred Amounts amount amount amount glyburide 0.25-25 0.5-20 0.75-15 ethanol 5-60 ⁇ 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-15 polyethylene glycol 0-60 30-45 35-40 water 2.5-30 5-20 6-15 flavors 0.1-5 1-4 2-3
  • Glyburide Non-polar Bite Capsule preferred most preferred Amounts amount amount amount glyburide 0.01-10 0.025-7.5 0.1-4 olive oil 30-60 35-55 30-50 polyoxyethylated oleic 30-60 35-55 30-50 glycerides flavors 0.1-5 1-4 2-3
  • Zidovudine Formally Called Azidothymidine (AZT) (Retrovir)
  • Non-polar Lingual Spray preferred most preferred Amounts amount amount amount zidovudine 10-50 15-40 25-35 Soya oil 20-85 25-70 30-40 Butane 15-80 30-75 60-70 flavors 0.1-5 1-4 2-3
  • D. zidovudine [Formerly Called Azidothymidine (AZT) (Retrovir)] Lingual Spray most Amounts preferred amount preferred amount zidovudine 10-50 15-40 25-35 water 30-80 40-75 45-70 ethanol 5-20 7.5-15 9.5-12.5 polyethylene glycol 5-20 7.5-15 9.5-12.5 flavors 0.1-5 1-4 2-3
  • Ondansetron Hydrochloride Lingual Spray most Amounts preferred amount preferred amount ondansetron 1-25 2-20 2.5-15 hydrochloride citric acid 1-10 2-8 2.5-5 monohydrate sodium citrate 0.5-5 1-4 1.25-2.5 dihydrate water 1-90 5-85 10-75 ethanol 5-30 7.5-20 9.5-15 propylene glycol 5-30 7.5-20 9.5-15 polyethylene glycol 5-30 7.5-20 9.5-15 flavors 1-10 3-8 5-7.5
  • C. Dimenhydrinate Polar Lingual Spray most Amounts preferred amount preferred amount dimenhydrinate 3-50 4-40 5-35 water 5-90 10-80 15-75 ethanol 1-80 3-50 5-10 polyethylene glycol 1-80 3-50 5-15 sorbitol 0.1-5 0.2-40 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
  • Cimetidine Hydrochloride Bite Capsule most Amounts preferred amount preferred amount cimetidine HCl 10-60 15-55 25-50 glycerin 5-20 7.5-15 10-12.5 polyethylene glycol 20-90 25-85 30-75 flavors 1-10 2-8 3-6
  • Famotidine Lingual Spray most Amounts preferred amount preferred amount famotidine 1-35 5-30 7-20 water 2.5-25 3-20 5-10 L-aspartic acid 0.1-20 1-15 5-10 polyethylene glycol 20-97 30-95 50-85 flavors 0.1-10 1-7.5 2-5
  • Famotidine Non-polar Lingual Spray most Amounts preferred amount preferred amount famotidine 1-35 5-30 7-20 Soya oil 10-50 15-40 15-20 Butanel 5-80 30-75 45-70 polyoxyethylated 10-50 15-40 15-20 oleic glycerides flavors 0.1-5 1-4 2-3
  • Phenytoin Sodium Lingual Spray most Amounts preferred amount preferred amount phenytoin sodium 10-60 15-55 20-40 water 2.5-25 3-20 5-10 ethanol 5-30 7.5-20 9.5-15 propylene glycol 5-30 7.5-20 9.5-15 polyethylene glycol 5-30 7.5-20 9.5-15 flavors 1-10 3-8 5-7.5
  • Phenytoin Non-polar Lingual Spray most Amounts preferred amount preferred amount phenytoin 5-45 10-40 15-35 migylol 10-50 15-40 15-20 Butane 15-80 30-75 60-70 polyoxyethylated 10-50 15-40 15-20 oleic glycerides flavors 0.1-10 1-8 5-7.5
  • Carboprost Thromethamine Lingual Spray most Amounts preferred amount preferred amount carboprost 0.05-5 0.1-3 0.25-2.5 thromethamine water 50-95 60-80 65-75 ethanol 5-20 7.5-15 9.5-12.5 polyethylene glycol 5-20 7.5-15 9.5-12.5 sodium chloride 1-20 3-15 4-8 flavors 0.1-5 1-4 2-3
  • valerian as Lingual Spray most preferred Amounts preferred amount amount valerian extract 0.1-10 0.2-7 0.25-5 water 50-95 60-80 65-75 ethanol 5-20 7.5-15 9.5-12.5 polyethylene glycol 5-20 7.5-15 9.5-12.5 flavors 1-10 2-8 3-6
  • Echinacea as Bite Capsule most preferred Amounts preferred amount amount echinacea extract 30-85 40-75 45-55 soya oil 7.5-50 10-40 12.5-35 soya lecithin 0.001-1.0 0.005-0.5 .01-0.1 Soya fats 7.5-50 10-40 12.5-35 flavors 1-10 2-8 3-6
  • A. Diphenhydramine Hydrochloride Lingual Spray most preferred Amounts preferred amount amount diphenhydramine 3-50. 4-40 5-35 HCl water 5-90 10-80 50-75 ethanol 1-80 3-50 5-10 polyethylene glycol 1-80 3-50 5-15 Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
  • Isoproterenol Hydrochloride as Polar Lingual Spray most preferred Amounts preferred amount amount isoproterenol Hydrochloride 0.1-10 0.2-7.5 0.5-6 water 5-90 10-80 50-75 ethanol 1-80 3-50 5-10 polyethylene glycol 1-80 3-50 5-15 Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
  • C. Terbutaline as Non-polar Lingual Spray most preferred Amounts preferred amount amount terbutaline 0.1-10 0.2-7.5 0.5-6 migylol 25-50 30-45 35-40 isobutane 5-60 10-50 20-35 polyoxyethylated 25-50 30-45 35-40 oleic glycerides flavors 0.1-10 1-8 5-7.5
  • Theophylline Polar Bite Capsule most preferred Amounts preferred amount amount theophylline 5-50 10-40 15-30 polyethylene glycol 20-60 25-50 30-40 glycerin 25-50 35-45 30-40 propylene glycol 25-50 35-45 30-40 flavors 0.1-5 1-4 2-3
  • Prostaglandin E (Vasodilator) Most-Preferred Amount Preferred Amount Amount prostaglandin E 1 0.01-10% 0.1-5% 0.2-3% Ethanol 10-90% 20-75% 25-50% Propylene glycol 1-90% 5-80% 10-75% Water 0.01-5% 0.1-4% 0.2-2% Flavors 0.05-10% 0.1-5% 0.1-2.5% Propellant 2-10% 3-5% 3-4%
  • Promethazine Antiemetic, Sleep Inducer, and CNS Active Amine

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Addiction (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Anesthesiology (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Psychiatry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Rheumatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, active compound, and optional flavoring agent; formulation II: aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation III: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application is a continuation-in-part of application No. 09/537,118, filed Mar. 29, 2000 which is a continuation-in-part of the U.S. national phase designation of PCT/US97/17899 filed Oct. 1, 1997, the disclosures of which are incorporated by reference herein in their entirety.[0001]
    • BACKGROUND OF THE INVENTION
  • It is known that certain biologically active compounds are better absorbed through the oral mucosa than through other routes of administration, such as through the stomach or intestine. However, formulations suitable for such administration by these latter routes present their own problems. For example, the biologically active compound must be compatible with the other components of the composition such as propellants, solvents, etc. Many such formulations have been proposed. For example, U.S. Pat. No. 4,689,233, Dvorsky et al., describes a soft gelatin capsule for the administration of the anti-coronary drug nifedipine dissolved in a mixture of polyether alcohols. U.S. Pat. No. 4,755,389, Jones et al., describes a hard gelatin chewable capsule containing nifedipine. A chewable gelatin capsule containing a solution or dispersion of a drug is described in U.S. Pat. No. 4,935,243, Borkan et al. U.S. Pat. No. 4,919,919, Aouda et al, and U.S. Pat. No. 5,370,862, Klokkers-Bethke, describe a nitroglycerin spray for administration to the oral mucosa comprising nitroglycerin, ethanol, and other components. An orally administered pump spray is described by Cholcha in U.S. Pat. No. 5,186,925. Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. Pat. No. 3,155,574, Silson et al., U.S. Pat. No. 5,011,678, Wang et al., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered. [0002]
    • SUMMARY OF THE INVENTION
  • A buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. [0003]
  • The buccal aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable non-polar solvent comprise in weight % of total composition: pharmaceutically acceptable propellant 5-80%, nonpolar solvent 19-85%, active compound 0.05-50%, suitably additionally comprising, by weight of total composition a flavoring agent 0.01-10%. Preferably the composition comprises: propellant 10-70%, non-polar solvent 25-89.9%, active compound 0.01-40%, flavoring agent 1-8%; most suitably propellant 20-70%, non-polar solvent 25-74.75%, active compound 0.25-35%, flavoring agent 2-7.5%. [0004]
  • The buccal polar aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent are also administrable in aerosol form driven by a propellant. In this case, the composition comprises in weight % of total composition: aqueous polar solvent 10-97%, active compound 0.1-25%, suitably additionally comprising, by weight of total composition a flavoring agent 0.05-10% and propellant: 2-10%. Preferably the composition comprises: polar solvent 20-97%, active compound 0.1-15%, flavoring agent 0.1-5% and propellant 2-5%; most suitably polar solvent 25-97%, active compound 0.2-25%, flavoring agent 0.1-2.5% and propellant 2-4%. [0005]
  • The buccal pump spray composition of the present invention, i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound wherein said active compound is soluble in a pharmacologically acceptable non-polar solvent comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, and suitably additionally, flavoring agent 0.1-10%. [0006]
  • The buccal polar pump spray compositions of the present invention, i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent comprises in weight % of total composition: aqueous polar solvent 30-99.69%, active compound 0.001-60%, suitably additionally comprising, by weight of total composition a flavoring agent 0.1-10%. Preferably the composition comprises: polar solvent 37-98.58%, active compound 0.005-55%, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01-40%, flavoring agent 0.75-7.5%. [0007]
  • The soft bite gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable non-polar solvent, having charged thereto a fill composition comprise in weight % of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01-80%, provided that said fill composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 0.01-10%. Preferably, the soft bite gelatin capsule comprises: non-polar solvent 21.5-99.975%, emulsifier 0-15%, active compound 0.025-70%, flavoring agent 1-8%; most suitably: nonpolar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1-65.0%, flavoring agent 2-6%. [0008]
  • The soft bite polar gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable polar solvent, having charged thereto a composition comprising in weight % of total composition: polar solvent 25-99.89%, emulsifier 0-20%, active compound 0.01-65%, provided that said composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 01-10%. Preferably, the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0-15%, active compound 0.025-55%, flavoring agent 1-8%; most suitably: polar solvent 44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%. [0009]
  • It is an object of the invention to coat the mucosal membranes either with extremely fine droplets of spray containing the active compounds or a solution or paste thereof from bite capsules. [0010]
  • It is also an object of the invention to administer to the oral mucosa of a mammalian in need of same, preferably man, by spray or bite capsule, a predetermined amount of a biologically active compound by this method or from a soft gelatin capsule. [0011]
  • A further object is a sealed aerosol spray container containing a composition of the non polar or polar aerosol spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition. [0012]
  • As the propellant evaporates after activation of the aerosol valve, a mist of fine droplets is formed which contains solvent and active compound. [0013]
  • The propellant is a non-Freon material, preferably a C[0014] 3-8 hydrocarbon of a linear or branched configuration. The propellant should be substantially non-aqueous. The propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.
  • The non-polar solvent is a non-polar hydrocarbon, preferably a C[0015] 7-18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol. The solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at a temperature of 0-40° C. a pressure range of between 1-3 atm.
  • The polar and non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, which does not allow entry of atmospheric gasses with each activation. Such containers are commercially available. [0016]
  • A further object is a pump spray container containing a composition of the pump spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition. [0017]
  • A further object is a soft gelatin bite capsule containing a composition of as set forth above. The formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.) [0018]
  • The polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound. The solvent preferably dissolves the active compound. However, other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill. [0019]
  • Soft gelatin capsules are well known in the art. See, for example, U.S. Pat. No. 4,935,243, Borkan et al., for its teaching of such capsules. The capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds. Typical capsules, which are swallowed whole or bitten and then swallowed, deliver the active compounds to the stomach, which results in significant lag time before maximum blood levels can be achieved or subject the compound to a large first pass effect. Because of the enhanced absorption of the compounds through the oral mucosa and no chance of a first pass effect, use of the bite capsules of the invention will eliminate much of the lag time, resulting in hastened onset of biological effect. The shell of a soft gelatin capsule of the invention may comprise, for example: gelatin: 50-75%, glycerin 20-30%, colorants 0.5-1.5%, water 5-10%, and sorbitol 2-10%. [0020]
  • The active compound may include, biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals. [0021]
  • The active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application. [0022]
  • The active compounds may also include nerve impulse inhibitors, anti-opioid agents, anti-migraine agents, anti-muscle spasm agents, pain control agents, anesthetics, anti-inflammatory drugs, or mixtures thereof.[0023]
    • BRIEF DESCRIPTION OF THE DRAWING
  • FIG. 1. is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.[0024]
    • DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • The preferred active compounds of the present invention are in an ionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or pump spray compositions, they are soluble in the spray solvent). These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) first pass effect. [0025]
  • As propellants for the non polar sprays, propane, N-butane, iso-butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used. N-butane and iso-butane, as single gases, are the preferred propellants. It is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1-0.2%. All percentages herein are by weight unless otherwise indicated. It is also preferable that the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The concentration of each of these should be less than 0.1%, except that water may be as high as 0.2%. [0026]
  • Suitable non-polar solvents for the capsules and the non-polar sprays include (C[0027] 2-C24) fatty acid (C2-C6) esters, C7-C 18 hydrocarbon, C2-C6 alkanoyl esters, and the triglycerides of the corresponding acids. When the capsule fill is a paste, other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.
  • As solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C[0028] 2-C8) mono and polyols and alcohols of C7-C18 linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • It is expected that some glycerin and water used to make the gelatin shell will migrate from the shell to the fill during the curing of the shell. Likewise, there may be some migration of components from the fill to the shell during curing and even throughout the shelf-life of the capsule. [0029]
  • Therefore, the values given herein are for the compositions as prepared, it being within the scope of the invention that minor variations will occur. [0030]
  • The preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc.), and combinations thereof. [0031]
  • The active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, octreotide acetate, calcitonin-salmon, insulin lispro, sumatriptan succinate, clozepine, cyclobenzaprine, dexfenfluramine hydrochloride, glyburide, zidovudine, erythromycin, ciprofloxacin, ondansetron hydrochloride, dimenhydrinate, cimetidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thromethamine, carboprost, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate and neutraceuticals, that is to say nutrients with pharmacological action such as but not limited to carnitine, valerian, echinacea, and the like. [0032]
  • In another embodiment, the active compound is a nerve impulse inhibitor, anti-opioid agent, anti-migraine agent, anti-muscle spasm agent, pain control agent, anesthetic, anti-inflammatory drug, or a mixture thereof. [0033]
  • In one embodiment the active compound is a nerve impulse inhibitor. Suitable nerve impulse inhibitors for use in the buccal sprays of the invention include, but are not limited to levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxacurium, mivacurium, pancuronium, vecuronium, pipecuronium, rocuronium, and mixtures thereof. [0034]
  • In one embodiment the active compound is an anti-opioid agent. Suitable anti-opioid agents for use in the buccal sprays of the invention include, but are not limited to, naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof. [0035]
  • In one embodiment the active compound is an anti-migraine agent. Suitable anti-migraine agents for use in the buccal sprays of the invention include, but are not limited to, frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof. [0036]
  • In one embodiment the active compound is an anti-muscle spasm agent. Suitable anti-muscle spasm agents for use in the buccal sprays of the invention include, but are not limited to, baclofen, botulinum toxin, carisoprodol, chlorphenesin, chlorzoxazone, cyclobenzaprine, dantrolene, diazepam, metaxalone, methocarbamol, orphenadrine, tizanidine, and mixtures thereof. [0037]
  • In one embodiment the active compound is a pain control agent. Suitable pain control agents for use in the buccal sprays of the invention include, but are not limited to, non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof. [0038]
  • In one embodiment the active compound is an anesthetic. Suitable anesthetics for use in the buccal sprays of the invention include, but are not limited to, benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof. [0039]
  • In one embodiment the active compound is an anti-inflammatory drug. Suitable anti-inflammatory drugs for use in the buccal sprays of the invention include, but are not limited to, alosetron, anakinra, beclomethasone, betamethasone, budesonide, clobetasol, celecoxib, cromolyn, desoximetasone, dexamethasone, epinastic, etanercept, etoricoxib, flunisolide, fluocinonide, fluticasone, formoterol, hydrocortisone, hydroxychloroquine, ibudilast, ketotifen, meloxicam, mesalamine, methotrexate, methylprednisolone, mometasone, montelukast, nedocromil, olsalazine, prednisone, ramatroban, rofecoxib, salsalate, terbutaline, triamcinolone, valdecoxib, zafirlukast, and mixtures thereof. [0040]
  • The formulations of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof. The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases. [0041]
  • When an active compound of the present invention is acidic, salts may be prepared from pharmaceutically acceptable non-toxic bases. Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins such as arginine, betaine, caffeine, choline, N,N dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl-aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl-glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc. [0042]
  • When an active compound of the present invention is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane-sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc. Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids. [0043]
  • In the discussion of methods of treatment herein, reference to the active compounds is meant to also include the pharmaceutically acceptable salts thereof. While certain formulations are set forth herein, the actual amounts to be administered to the mammal or man in need of same are to be determined by the treating physician. [0044]
  • The invention is further defined by reference to the following examples, which are intended to be illustrative and not limiting. [0045]
  • The following are examples of certain classes. All values unless otherwise specified are in weight percent. [0046]
    • EXAMPLES Example 1 Biologically Active Peptides Including Peptide Hormones
  • A. Cyclosporine Lingual Spray [0047]
    preferred most preferred
    Amounts amount amount
    cyclosporine 5-50 10-35 15-25
    water 5-20 7.5-50  9.5-12 
    ethanol 5-60 7.5-50  10-20
    polyethylene glycol 20-60  30-45 35-40
    flavors 0.1-5   1-4 2-3
  • B. Cyclosporine Non-Polar Lingual Spray [0048]
    preferred most preferred
    Amounts amount amount
    cyclosporine  1-50  3-40  5-30
    Migylol 20 25 30-40
    Polyoxyethylated castor oil 20 25 30-40
    Butane 25-80 30-70 33-50
    flavors 0.1-5   1-4 2-3
  • C. Cyclosporine Non-polar Bite Caosule [0049]
    preferred most preferred
    Amounts amount amount
    cyclosporine  1-35 5-25 10-20
    olive oil 25-60 35-55  30-45
    polyoxyethylated 25-60 35-55  30-45
    oleic glycerides
    flavors 0.1-5   1-4  2-3
  • D. Cyclosporine Bite Capsule [0050]
    preferred most preferred
    Amounts amount amount
    cyclosporine 5-50 10-35 15-25
    polyethylene glycol 20-60  30-45 35-40
    glycerin 5-30 7.5-25  10-20
    propylene glycol 5-30 7.5-25  10-20
    flavors 0.1-10   1-8 3-6
  • E. Sermorelin (as the Acetate) Lingual Spray [0051]
    preferred
    Amounts amount most preferred
    sermorelin (as the acetate) .01-5 .1-3    .2-1.0
    mannitol   1-25 5-20 10-15
    monobasic sodium phosphate, 0.1-5  1-3.1  .5-2.5
    dibasic sodium phosphate water 0.01-5  .05-3   0.1-0.5
    ethanol   5-30 7.5-25   9.5-15 
    polyethylene glycol   20-60 30-45  35-40
    propylene glycol   5-25 10-20  12-17
    flavors 0.1-5 1-4  2-3
  • F. Octreotide Acetate (Sandostatin) Lingual Spray [0052]
    preferred most preferred
    Amounts amount amount
    octreotide acetate 0.001-0.5   0.005-0.250 0.01-0.10
    acetic acid 1-10 2-8 4-6
    sodium acetate 1-10 2-8 4-6
    sodium chloride 3-30  .5-25  15-20
    flavors 0.1-5   0.5-.4  2-3
    ethanol 5-30 7.5-20  9.5-15 
    water 15-95  35-90 65-85
    flavors 0.1-5   1-4 2-3
  • G. Calcitonin-salmon Lingual Spray [0053]
    preferred most preferred
    Amounts amount amount
    calcitonin-salmon 0.001-5    0.005-2    01-1.5
    ethanol 2-15 3-10  7-9.5
    water 30-95  50-90  60-80 
    polyethylene glycol 2-15 3-10  7-9.5
    sodium chloride 2.5-20   5-15  10-12.5
    flavors 0.1-5   1-4  2-3 
  • H. Insulin Lispro, Lingual Spray [0054]
    preferred most preferred
    Amounts amount amount
    insulin 20-60    4-55 5-50
    glycerin 0.1-10   0.25-5  0.1-1.5 
    dibasic sodium 1-15 2.5-10 4-8 
    phosphate
    m-cresol, 1-25   5-25 7.5-12.5
    zinc oxide 0.01-0.25    .05-0.15 0.075-0.10 
    m-cresol 0.1-1    0.2-0.8 0.4-0.6 
    phenol trace amounts trace amounts trace amounts
    ethanol 5-20 7.5-15 9-12
    water 30-90   40-80 50-75 
    propylene glycol 5-20 7.5-15 9-12
    flavors 0.1-5   0.5-3  0.75-2   
    • Example 2 CNS Active Amines and their Salts: Including but not Limited to Tricyclic Amines, GABA Analogues, Thiazides, Phenothiazine Derivatives, Serotonin Antagonists and Serotonin Reuptake Inhibitors
  • A. Sumatriptan Succinate Lingual Spray [0055]
    preferred most preferred
    Amounts amount amount
    sumatriptan succinate 0.5-30     1-20 10-15
    ethanol 5-60 7.5-50 10-20
    propylene glycol 5-30 7.5-20 10-15
    polyethylene glycol 0-60  30-45 35-40
    water 5-30 7.5-20 10-15
    flavors 0.1-5    1-4 2-3
  • B. Sumatriptan Succinate Bite Capsule [0056]
    preferred most preferred
    Amounts amount amount
    sumatriptan succinate 0.01-5   0.05-3.5  0.075-1.75 
    polyethylene glycol 25-70 30-60 35-50
    glycerin 25-70 30-60 35-50
    flavors 0.1-10  1-8 3-6
  • C. Clozepine Lingual Spray [0057]
    preferred most preferred
    Amounts amount amount
    clozepine 0.5-30     1-20 10-15
    ethanol 5-60 7.5-50 10-20
    propylene glycol 5-30 7.5-20 10-15
    polyethylene glycol 0-60  30-45 35-40
    water 5-30 7.5-20 10-15
    flavors 0.1-5    1-4 2-3
  • D. Clozepine Non-polar Lingual Spray with Propellant [0058]
    preferred most preferred
    Amounts amount amount
    clozepine 0.5-30 1-20 10-15
    Migylol  20-85 25-70  30-40
    Butanol   5-80 30-75  60-70
    flavors 0.1-5  1-4  2-3
  • E. Clozepine Non-polar Lingual Spray without Propellant [0059]
    preferred most preferred
    Amounts amount amount
    clozepine 0.5-30 1-20 10-15
    Migylol    70-99.5  80-99  85-90
    flavors 0.1-5  1-4  2-3
  • F. Cyclobenzaprine Non-polar Lingual Spray [0060]
    preferred most preferred
    Amounts amount amount
    cyclobenzaprine (base) 0.5-30 1-20 10-15
    Migylol  20-85 25-70  30-40
    Iso-butane  15-80 30-75  60-70
    flavors 0.1-5  1-4  2-3
  • G. Dexfenfluramine Hydrochloride Lingual Spray [0061]
    preferred most preferred
    Amounts amount amount
    dexfenfluramine Hcl 5-30 7.5-20 10-15
    ethanol 5-60 7.5-50 10-20
    propylene glycol 5-30 7.5-20 10-15
    polyethylene glycol 0-60  30-45 35-40
    water 5-30 7.5-20 10-15
    flavors 0.1-5    1-4 2-3
    • Example 3 Sulfonylureas
  • A. Glyburide Lingual Spray [0062]
    preferred most preferred
    Amounts amount amount
    glyburide 0.25-25   0.5-20 0.75-15  
    ethanol 5-60 −7.5-50   10-20
    propylene glycol 5-30 7.5-20 10-15
    polyethylene glycol 0-60  30-45 35-40
    water 2.5-30     5-20  6-15
    flavors 0.1-5    1-4 2-3
  • B. Glyburide Non-polar Bite Capsule [0063]
    preferred most preferred
    Amounts amount amount
    glyburide 0.01-10   0.025-7.5  0.1-4 
    olive oil 30-60 35-55  30-50
    polyoxyethylated oleic 30-60 35-55  30-50
    glycerides
    flavors 0.1-5   1-4  2-3
    • Example 4 Antibiotics Anti-fungals and Anti-virals
  • A. Zidovudine [Formerly Called Azidothymidine (AZT) (Retrovir)] Non-polar Lingual Spray [0064]
    preferred most preferred
    Amounts amount amount
    zidovudine 10-50 15-40 25-35
    Soya oil 20-85 25-70 30-40
    Butane 15-80 30-75 60-70
    flavors 0.1-5   1-4 2-3
  • B. Erythromycin Bite Capsule Bite Capsule [0065]
    preferred most preferred
    Amounts amount amount
    erythromycin 25-65  30-50 35-45
    polyoxyethylene glycol 5-70 30-60 45-55
    glycerin 5-20 7.5-15    10-12.5
    flavors 1-10 2-8 3-6
  • C. Ciprofloxacin Hydrochloride Bite Capsule [0066]
    preferred most preferred
    Amounts amount amount
    ciprofloxacin hydrochloride 25-65  35-55 40-50
    glycerin 5-20 7.5-15    10-12.5
    polyethylene glycol 120-75  30-65 40-60
    flavors 1-10 2-8 3-6
  • D. zidovudine [Formerly Called Azidothymidine (AZT) (Retrovir)] Lingual Spray [0067]
    most
    Amounts preferred amount preferred amount
    zidovudine 10-50 15-40 25-35
    water 30-80 40-75 45-70
    ethanol  5-20 7.5-15   9.5-12.5
    polyethylene glycol  5-20 7.5-15   9.5-12.5
    flavors 0.1-5   1-4 2-3
    • Example 5 Anti-emetics
  • A. Ondansetron Hydrochloride Lingual Spray [0068]
    most
    Amounts preferred amount preferred amount
    ondansetron  1-25  2-20 2.5-15 
    hydrochloride
    citric acid  1-10 2-8 2.5-5  
    monohydrate
    sodium citrate 0.5-5   1-4 1.25-2.5 
    dihydrate
    water  1-90  5-85 10-75
    ethanol  5-30 7.5-20  9.5-15 
    propylene glycol  5-30 7.5-20  9.5-15 
    polyethylene glycol  5-30 7.5-20  9.5-15 
    flavors  1-10 3-8   5-7.5
  • B. Dimenhydrinate Bite Capsule [0069]
    most
    Amounts preferred amount preferred amount
    dimenhydrinate 0.5-30   2-25  3-15
    glycerin  5-20 7.5-15    10-12.5
    polyethylene glycol 45-95 50-90 55-85
    flavors  1-10 2-8 3-6
  • C. Dimenhydrinate Polar Lingual Spray [0070]
    most
    Amounts preferred amount preferred amount
    dimenhydrinate  3-50  4-40  5-35
    water  5-90 10-80 15-75
    ethanol  1-80  3-50  5-10
    polyethylene glycol  1-80  3-50  5-15
    sorbitol 0.1-5   0.2-40  0.4-1.0
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4 2-3
    • Example 6 Histamine H-2 Receptor Antagonists
  • A. Cimetidine Hydrochloride Bite Capsule [0071]
    most
    Amounts preferred amount preferred amount
    cimetidine HCl 10-60 15-55 25-50
    glycerin  5-20 7.5-15    10-12.5
    polyethylene glycol 20-90 25-85 30-75
    flavors  1-10 2-8 3-6
  • B. Famotidine Lingual Spray [0072]
    most
    Amounts preferred amount preferred amount
    famotidine  1-35  5-30  7-20
    water 2.5-25   3-20  5-10
    L-aspartic acid 0.1-20   1-15  5-10
    polyethylene glycol 20-97 30-95 50-85
    flavors 0.1-10    1-7.5 2-5
  • C. Famotidine Non-polar Lingual Spray [0073]
    most
    Amounts preferred amount preferred amount
    famotidine  1-35  5-30  7-20
    Soya oil 10-50 15-40 15-20
    Butanel  5-80 30-75 45-70
    polyoxyethylated 10-50 15-40 15-20
    oleic glycerides
    flavors 0.1-5   1-4 2-3
    • Example 7 Barbiturates
  • A. Phenytoin Sodium Lingual Spray [0074]
    most
    Amounts preferred amount preferred amount
    phenytoin sodium 10-60 15-55 20-40
    water 2.5-25   3-20  5-10
    ethanol  5-30 7.5-20  9.5-15 
    propylene glycol  5-30 7.5-20  9.5-15 
    polyethylene glycol  5-30 7.5-20  9.5-15 
    flavors  1-10 3-8   5-7.5
  • B. Phenytoin Non-polar Lingual Spray [0075]
    most
    Amounts preferred amount preferred amount
    phenytoin  5-45 10-40 15-35
    migylol 10-50 15-40 15-20
    Butane 15-80 30-75 60-70
    polyoxyethylated 10-50 15-40 15-20
    oleic glycerides
    flavors 0.1-10  1-8   5-7.5
    • Example 8 Prostaglandins
  • A. Carboprost Thromethamine Lingual Spray [0076]
    most
    Amounts preferred amount preferred amount
    carboprost 0.05-5   0.1-3   0.25-2.5 
    thromethamine
    water 50-95 60-80 65-75
    ethanol  5-20 7.5-15   9.5-12.5
    polyethylene glycol  5-20 7.5-15   9.5-12.5
    sodium chloride  1-20  3-15 4-8
    flavors 0.1-5   1-4 2-3
  • pH is Adjusted with Sodium Hydroxide and/or Hydrochloric Acid [0077]
  • B. Carboprost Non-polar Lingual Spray [0078]
    Amounts preferred amount most preferred amount
    carboprost 0.05-5   0.1-3   0.25-2.5 
    migylol 25-50 30-45 35-40
    Butane  5-60 10-50 20-35
    polyoxyethylated 25-50 30-45 35-40
    oleic glycerides
    flavors 0.1-10  1-8   5-7.5
    • Example 9 Neutraceuticals
  • A. Carnitine as Bite Capsule (Contents are a Paste) [0079]
    most preferred
    Amounts preferred amount amount
    carnitine fumarate 6-80 30-70   45-65
    soya oil 7.5-50   10-40 12.5-35
    soya lecithin 0.001-1.0   0.005-0.5    .01-0.1
    Soya fats 7.5-50   10-40 12.5-35
    flavors 1-10 2-8   3-6
  • B. Valerian as Lingual Spray [0080]
    most preferred
    Amounts preferred amount amount
    valerian extract 0.1-10   0.2-7  0.25-5 
    water 50-95   60-80   65-75
    ethanol 5-20 7.5-15   9.5-12.5
    polyethylene glycol 5-20 7.5-15   9.5-12.5
    flavors 1-10  2-8   3-6
  • C. Echinacea as Bite Capsule [0081]
    most preferred
    Amounts preferred amount amount
    echinacea extract  30-85 40-75   45-55
    soya oil 7.5-50 10-40 12.5-35
    soya lecithin 0.001-1.0    0.005-0.5    .01-0.1
    Soya fats 7.5-50 10-40 12.5-35
    flavors   1-10 2-8   3-6
  • D. Mixtures of Ingredients [0082]
    most preferred
    Amounts preferred amount amount
    magnesium oxide 15-40   20-35   25-30
    chromium picolinate 0.01-1.0   0.02-0.5   .025-0.75
    folic acid .025-3.0   0.05-2.0  0.25-0.5
    vitamin B-12 0.01-1.0   0.02-0.5   .025-0.75
    vitamin E 15-40   20-35   25-30
    Soya oil 10-40 12.5-35   15-20
    soya lecithin 0.1-5   0.2-4   0.5-1.5
    soya fat 10-40   15-35 17.5-20
    • Example 10 Sleep Inducers (also CNS Active Amine)
  • A. Diphenhydramine Hydrochloride Lingual Spray [0083]
    most preferred
    Amounts preferred amount amount
    diphenhydramine  3-50. 4-40 5-35
    HCl water 5-90 10-80  50-75 
    ethanol 1-80 3-50 5-10
    polyethylene glycol 1-80 3-50 5-15
    Sorbitol 0.1-5   0.2-4   0.4-1.0 
    aspartame 0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5   1-4  2-3 
    • Example 11 Anti-Asthmatics-Bronchodilators
  • A. Isoproterenol Hydrochloride as Polar Lingual Spray [0084]
    most
    preferred
    Amounts preferred amount amount
    isoproterenol Hydrochloride 0.1-10 0.2-7.5  0.5-6  
    water   5-90 10-80  50-75 
    ethanol   1-80 3-50 5-10
    polyethylene glycol   1-80 3-50 5-15
    Sorbitol 0.1-5  0.2-4   0.4-1.0 
    aspartame  0.01-0.5  0.02-0.4  0.04-0.1 
    flavors 0.1-5  1-4  2-3 
  • B. Terbutaline Sulfate as Polar Lingual Spray [0085]
    most preferred
    Amounts preferred amount amount
    terbutaline sulfate 0.1-10   0.2-7.5 0.5-6
    water   5-90   10-80   50-75
    ethanol   1-10   2-8 2.5-5
    Sorbitol 0.1-5  0.2-4   0.4-1.0
    aspartame  0.01-0.5   0.02-0.4  0.04-0.1
    flavors 0.1-5    1-4   2-3
  • C. Terbutaline as Non-polar Lingual Spray [0086]
    most preferred
    Amounts preferred amount amount
    terbutaline 0.1-10 0.2-7.5 0.5-6  
    migylol  25-50 30-45 35-40
    isobutane   5-60 10-50 20-35
    polyoxyethylated  25-50 30-45 35-40
    oleic glycerides
    flavors 0.1-10 1-8   5-7.5
  • D. Theophylline Polar Bite Capsule [0087]
    most preferred
    Amounts preferred amount amount
    theophylline  5-50 10-40 15-30
    polyethylene glycol 20-60 25-50 30-40
    glycerin 25-50 35-45 30-40
    propylene glycol 25-50 35-45 30-40
    flavors 0.1-5   1-4 2-3
  • E. Albuterol Sulfate as Polar Lingual Spray [0088]
    Amounts preferred amount most preferred amount
    albuterol sulfate 0.1-10   0.2-7.5 0.5-6
    water   5-90   10-80   50-75
    ethanol   1-10   2-8 2.5-5
    Sorbitol 0.1-5  0.2-4   0.4-1.0
    aspartame  0.01-0.5   0.02-0.4  0.04-0.1
    flavors 0.1-5    1-4   2-3
    • Example 12 Polar Solvent Formulations Using a Propellant
  • A. Sulfonylurea [0089]
    Amount Preferred Amount Most-Preferred Amount
    glyburide  0.1-25%  0.5-15% 0.6-10%
    Ethanol   40-99%   60-97%  70-97%
    Water 0.01-5%  0.1-4% 0.2-2% 
    Flavors 0.05-10% 0.1-5%  0.1-2.5%
    Propellant   2-10%   3-5%  3-4%
  • B. Prostaglandin E (Vasodilator) [0090]
    Most-Preferred
    Amount Preferred Amount Amount
    prostaglandin E1 0.01-10% 0.1-5% 0.2-3%
    Ethanol   10-90%   20-75%   25-50%
    Propylene glycol   1-90%   5-80%   10-75%
    Water 0.01-5%  0.1-4% 0.2-2%
    Flavors 0.05-10% 0.1-5%   0.1-2.5%
    Propellant   2-10%   3-5%   3-4%
  • C. Promethazine (Antiemetic, Sleep Inducer, and CNS Active Amine) [0091]
    Most-Preferred
    Amount Preferred Amount Amount
    promethazine 1-25% 3-15% 5-12%
    Ethanol 10-90%  20-75%  25-50% 
    Propylene glycol 1-90% 5-80% 10-75% 
    Water 0.01-5%    0.1-4%   0.2-2%  
    Flavors 0.05-10%   0.1-5%   0.1-2.5% 
    Propellant 2-10% 3-5%  3-4% 
  • D. Meclizine [0092]
    Most-Preferred
    Amount Preferred Amount Amount
    meclizine 1-25% 3-15% 5-12%
    Ethanol 1-15% 2-10% 3-6   
    Propylene glycol 20-98%  5-90% 10-85% 
    Water 0.01-5%    0.1-4%   0.2-2%  
    Flavors 0.05-10%   0.1-5%   0.1-2.5% 
    Propellant 2-10% 3-5%  3-4% 

Claims (55)

What is claimed is:
1. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount of between 0.001 and 60 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and
a polar solvent in an amount between 30 and 99 percent by weight of the total composition.
2. The composition of claim 1, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
3. The composition of claim 2, wherein the polar solvent is present in an amount between 37 and 98 percent by weight of the total composition, the active compound is present in an amount between 0.005 and 55 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.5 and 8 percent by weight of the total composition.
4. The composition of claim 3, wherein the polar solvent is present in an amount between 60 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.01 and 40 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.75 and 7.5 percent by weight of the total composition.
5. The composition of claim 1, wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C2 to C8 mono- and poly-alcohols, and C7 to C18, alcohols of linear or branched configuration.
6. The composition of claim 1, wherein the polar solvent comprises aqueous polyethylene glycol.
7. The composition of claim 1, wherein the polar solvent comprises aqueous ethanol.
8. The composition of claim 1, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
9. The composition of claim 1, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
10. The composition of claim 1, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
11. The composition of claim 1, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
12. The composition of claim 2, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
13. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 1.
14. The method of claim 13, wherein the amount of the spray is predetermined.
15. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount of between 0.1 and 25 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof;
a polar solvent in an amount between 10 and 97 percent by weight of the total composition; and
a propellant in an amount between 2 and 10 percent by weight of the total composition, wherein said propellant is a C3 to C8 hydrocarbon of linear or branched configuration.
16. The composition of claim 15, further comprising a flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.
17. The composition of claim 16, wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.1 and 15 percent by weight of the total composition, the propellant is present in an amount between 2 and 5 percent by weight of the composition, and the flavoring agent is present in an amount between 0.1 and 5 percent by weight of the total composition.
18. The composition of claim 17, wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.2 and 25 percent by weight of the total composition, the propellant is present in an amount between 2 and 4 percent by weight of the composition, and flavoring agent is present in an amount between 0.1 and 2.5 percent by weight of the total composition.
19. The composition of claim 15, wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C2 to C8 mono- and poly-alcohols, and C7 to C18 alcohols of linear or branched configuration.
20. The composition of claim 19, wherein the polar solvent comprises aqueous polyethylene glycol.
21. The composition of claim 19, wherein the polar solvent comprises aqueous ethanol.
22. The composition of claim 15, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
23. The composition of claim 15, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
24. The composition of claim 15, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
25. The composition of claim 15, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
26. The composition of claim 16, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
27. The composition of claim 15, wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.
28. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 15.
29. The method of claim 28, wherein the amount of the spray is predetermined.
30. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount between 0.005 and 55 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and
a non-polar solvent in an amount between 30 and 99 percent by weight of the total composition.
31. The composition of claim 30, further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition.
32. The composition of claim 30, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
33. The composition of claim 30, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
34. The composition of claim 30, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
35. The composition of claim 30, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
36. The composition of claim 31, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
37. The composition of claim 30, wherein the solvent is selected from the group consisting of (C2-C24) fatty acid (C2-C6) esters, C7-C18 hydrocarbons of linear or branched configuration, C2-C6 alkanoyl esters, and triglycerides of C2-C6 carboxylic acids.
38. The composition of claim 37, wherein the solvent is miglyol.
39. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 30.
40. The method of claim 39, wherein the amount of the spray is predetermined.
41. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount between 0.05 and 50 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and
a non-polar solvent in an amount between 19 and 85 percent by weight of the total composition; and
a propellant in an amount between 5 and 80 percent by weight of the total composition, wherein said propellant is a C3 to C8 hydrocarbon of linear or brancehed configuration.
42. The composition of claim 41, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
43. The composition of claim 42, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
44. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising:
an active compound in an amount between 0.01 and 40 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and
a non-polar solvent in an amount between 25 and 89 percent by weight of the total composition;
a propellant in an amount between 10 and 70 percent by weight of the total composition, wherein said propellant is a C3 to C8 hydrocarbon of linear or brancehed configuration; and
A flavoring agent is present in an amount between 1 and 8 percent by weight of the total composition.
45. The composition of claim 44, wherein the propellant is present in an amount between 20 and 70 percent by weight of the total composition, the non-polar solvent is present in an amount between 25 and 75 percent by weight of the total composition, the active compound is present in an amount from between 0.25 and 35 percent by weight of the total composition, and the flavoring agent is present in an amount between 2 and 7.5 percent by weight of the total composition.
46. The composition of claim 42, wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pantane, iso-pentane, neo-pentane, and mixtures thereof.
47. The composition of claim 46, wherein the propellant is n-butane or iso-butane and has a water content of not more than 0.2 percent and a concentration of oxidizing agents, reducing agents, Lewis acids, and Lewis bases of less than 0.1 percent.
48. The composition of claim 41, wherein the solvent is selected from the group consisting of (C2-C24) fatty acid (C2-C6) esters, C7-C18 hydrocarbons of linear or branched configuration, C2-C6 alkanoyl esters, and triglycerides of C2-C6 carboxylic acids.
49. The composition of claim 48, wherein the solvent is miglyol.
50. The composition of claim 41, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
51. The composition of claim 41, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
52. The composition of claim 41, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
53. The composition of claim 41, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocaine, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
54. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim 41.
55. The method of claim 54, wherein the amount of the spray is predetermined.
US10/230,059 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating pain Abandoned US20030185761A1 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
US10/230,059 US20030185761A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
CA002497268A CA2497268A1 (en) 2002-08-29 2003-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
EP03811212A EP1539107A2 (en) 2002-08-29 2003-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
JP2004551444A JP2006505611A (en) 2002-08-29 2003-08-27 Oral, polar and non-polar sprays or capsules containing pain medications
PCT/US2003/026859 WO2004043428A2 (en) 2002-08-29 2003-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
NZ539284A NZ539284A (en) 2002-08-29 2003-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
AU2003296899A AU2003296899A1 (en) 2002-08-29 2003-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US10/671,710 US20040136913A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing sumatriptan
US10/726,625 US6969508B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US11/366,663 US20060165604A1 (en) 1997-10-01 2006-03-03 Buccal, polar and non-polar spray containing sumatriptan
US12/351,576 US20090162298A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray containing sumatriptan
US12/351,606 US20090124554A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US13/467,441 US20120252846A1 (en) 1997-10-01 2012-05-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
PCT/US1997/017899 WO1999016417A1 (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule
US53711800A 2000-03-29 2000-03-29
US10/230,059 US20030185761A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating pain

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US53711800A Continuation-In-Part 1997-10-01 2000-03-29

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US10/671,710 Continuation-In-Part US20040136913A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing sumatriptan
US10/726,625 Division US6969508B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US12/351,606 Continuation US20090124554A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain

Publications (1)

Publication Number Publication Date
US20030185761A1 true US20030185761A1 (en) 2003-10-02

Family

ID=32312002

Family Applications (4)

Application Number Title Priority Date Filing Date
US10/230,059 Abandoned US20030185761A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US10/726,625 Expired - Fee Related US6969508B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US12/351,606 Abandoned US20090124554A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US13/467,441 Abandoned US20120252846A1 (en) 1997-10-01 2012-05-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain

Family Applications After (3)

Application Number Title Priority Date Filing Date
US10/726,625 Expired - Fee Related US6969508B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US12/351,606 Abandoned US20090124554A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US13/467,441 Abandoned US20120252846A1 (en) 1997-10-01 2012-05-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain

Country Status (7)

Country Link
US (4) US20030185761A1 (en)
EP (1) EP1539107A2 (en)
JP (1) JP2006505611A (en)
AU (1) AU2003296899A1 (en)
CA (1) CA2497268A1 (en)
NZ (1) NZ539284A (en)
WO (1) WO2004043428A2 (en)

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20030077227A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20040062716A1 (en) * 1997-10-01 2004-04-01 Novadel Pharma Inc. Buccal, polar and non-polar spray of capsule
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
WO2004080382A3 (en) * 2003-03-11 2005-03-24 Sirus Pharmaceuticals Ltd Novel compositions containing fentanyl
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US20050226925A1 (en) * 2004-02-17 2005-10-13 Transoral Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20060002989A1 (en) * 2004-06-10 2006-01-05 Ahmed Salah U Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same
US20060062812A1 (en) * 2003-03-11 2006-03-23 Calvin Ross Novel compositions
US20060159624A1 (en) * 1997-10-01 2006-07-20 Dugger Harry A Iii Buccal, polar and non-polar spray containing zolpidem
US20060198790A1 (en) * 1997-10-01 2006-09-07 Dugger Harry A Iii Buccal, polar and non-polar spray containing ondansetron
WO2006105205A1 (en) * 2005-03-29 2006-10-05 University Of Kentucky Research Foundation Sublingual spray for the treatment of pain
US20060222597A1 (en) * 1997-10-01 2006-10-05 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20060240050A1 (en) * 2003-07-23 2006-10-26 Douglas Pharmaceuticals Limited Stable clozapine suspension formulation
US20060276501A1 (en) * 2005-05-25 2006-12-07 Transoral Pharmaceuticals, Inc. Solid compositions for treating middle-of-the-night insomnia
US20070225322A1 (en) * 2005-05-25 2007-09-27 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the night insomnia
US20070287740A1 (en) * 2005-05-25 2007-12-13 Transcept Pharmaceuticals, Inc. Compositions and methods of treating middle-of-the night insomnia
US20080171089A1 (en) * 2006-12-22 2008-07-17 Blondino Frank E Stable anti-nausea oral spray formulations and methods
US20080280947A1 (en) * 2007-05-10 2008-11-13 Blondino Frank E Anti-insomnia compositions and methods
US20090162298A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing sumatriptan
WO2011036521A2 (en) 2009-09-25 2011-03-31 Dr. Reddy's Laboratories Limited Formulations comprising triptan compounds
KR20120028349A (en) * 2009-05-29 2012-03-22 모리시타 진탄 가부시키가이샤 Oral medicinal composition and oral medicinal capsule having the composition encapsulated therein
WO2014033680A1 (en) * 2012-08-31 2014-03-06 Assistance Publique - Hopitaux De Paris Gelling formulation containing ketamine
EP2767163A1 (en) 2005-02-17 2014-08-20 Abbott Laboratories Transmucosal administration of drug compositions for treating and preventing disorders in animals
EP2801358A3 (en) * 2006-05-08 2015-03-04 Arturo Solis Herrera The use of nicotine for diminishing pain in renal region in humans
CN105193774A (en) * 2015-09-21 2015-12-30 山东新时代药业有限公司 Sevoflurane inhalant
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US9707184B2 (en) 2014-07-17 2017-07-18 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10195153B2 (en) 2013-08-12 2019-02-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10357464B2 (en) * 2006-09-20 2019-07-23 The Board Of Regents Of The University Of Texas System Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief
US10420720B2 (en) * 2008-01-22 2019-09-24 The Board Of Regents Of The University Of Texas System Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief
US10959958B2 (en) 2014-10-20 2021-03-30 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form
CN113350277A (en) * 2021-06-30 2021-09-07 广东科伦药业有限公司 Mesalazine gargle for treating chemotherapy oral mucositis and preparation method thereof
US11337962B2 (en) 2009-09-25 2022-05-24 Upsher-Smith Laboratories, Llc Formulations comprising triptan compounds
US11975096B2 (en) 2014-07-08 2024-05-07 Hikma Pharmaceuticals Usa Inc. Liquid naloxone spray

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090162300A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing alprazolam
US20030185761A1 (en) * 1997-10-01 2003-10-02 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
WO2006093786A2 (en) * 2005-02-25 2006-09-08 University Of Kentucky Research Foundation Scopolamine sublingual spray
CA2620364A1 (en) 2005-08-26 2007-03-01 David C. Yeomans Methods for treatment of headaches by administration of oxytocin
US9066847B2 (en) * 2007-01-05 2015-06-30 Aceirx Pharmaceuticals, Inc. Storage and dispensing devices for administration of oral transmucosal dosage forms
US8753308B2 (en) 2006-01-06 2014-06-17 Acelrx Pharmaceuticals, Inc. Methods for administering small volume oral transmucosal dosage forms using a dispensing device
US8202535B2 (en) 2006-01-06 2012-06-19 Acelrx Pharmaceuticals, Inc. Small-volume oral transmucosal dosage forms
US9289583B2 (en) * 2006-01-06 2016-03-22 Acelrx Pharmaceuticals, Inc. Methods for administering small volume oral transmucosal dosage forms using a dispensing device
US8865743B2 (en) * 2006-01-06 2014-10-21 Acelrx Pharmaceuticals, Inc. Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain
US8252329B2 (en) 2007-01-05 2012-08-28 Acelrx Pharmaceuticals, Inc. Bioadhesive drug formulations for oral transmucosal delivery
US8357114B2 (en) 2006-01-06 2013-01-22 Acelrx Pharmaceuticals, Inc. Drug dispensing device with flexible push rod
US8535714B2 (en) 2006-01-06 2013-09-17 Acelrx Pharmaceuticals, Inc. Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain
US8252328B2 (en) * 2006-01-06 2012-08-28 Acelrx Pharmaceuticals, Inc. Bioadhesive drug formulations for oral transmucosal delivery
NZ569949A (en) 2006-01-25 2011-10-28 Insys Therapeutics Inc Sublingual fentanyl spray
WO2007123955A2 (en) * 2006-04-19 2007-11-01 Novadel Pharma Inc. Stable hydroalcoholic oral spray formulations and methods
US20070260491A1 (en) * 2006-05-08 2007-11-08 Pamela Palmer System for delivery and monitoring of administration of controlled substances
US20070299687A1 (en) * 2006-06-23 2007-12-27 Pamela Palmer Inpatient system for patient-controlled delivery of oral transmucosal medications dosed as needed
EP2068831A4 (en) * 2006-07-28 2010-07-21 Novadel Pharma Inc Anti-migraine oral spray formulations and methods
SI2124556T1 (en) 2006-10-09 2015-01-30 Charleston Laboratories, Inc. Pharmaceutical compositions
ES2668366T3 (en) 2007-08-02 2018-05-17 Insys Development Company, Inc. Sublingual fentanyl spraying
US7985325B2 (en) * 2007-10-30 2011-07-26 Novellus Systems, Inc. Closed contact electroplating cup assembly
DE102007063040A1 (en) 2007-12-28 2009-07-23 Atotech Deutschland Gmbh Production of micro-reactors comprises coating a plate having channels and joint regions on the surface with a joining layer, applying a layer made from a suspension containing catalyst support particles and further processing
ES2620672T3 (en) 2008-01-09 2017-06-29 Charleston Laboratories, Inc. Double layer tablets comprising oxycodone and promethazine
EP2244783B1 (en) * 2008-01-22 2019-12-18 Board Of Regents, The University Of Texas System Volatile anesthetic compositions and methods of use
US8945592B2 (en) 2008-11-21 2015-02-03 Acelrx Pharmaceuticals, Inc. Sufentanil solid dosage forms comprising oxygen scavengers and methods of using the same
EP2451274B1 (en) 2009-07-08 2017-10-04 Charleston Laboratories, Inc. Pharmaceutical compositions
US8357398B2 (en) * 2009-10-21 2013-01-22 Alitair Pharmaceuticals Inc. Benzonatate compositions and methods of use
CN102770152B (en) 2009-11-25 2016-07-06 阿瑞斯根股份有限公司 The mucosal delivery of peptides
GB2476494A (en) * 2009-12-24 2011-06-29 Norwich Pharma Technologies Ltd Formulation for the sublingual delivery of sufentanil
EP2526971A1 (en) 2011-05-25 2012-11-28 ArisGen SA Mucosal delivery of drugs
CA2906072C (en) 2013-03-15 2023-01-10 Vapogenix, Inc. Analgesic compositions comprising halogenated volatile compounds
US9433644B2 (en) 2013-07-25 2016-09-06 Rutgilli Pharmaceuticals, Llc Formulations and methods for treating oral inflammation, injury, or pain
EP3082816B1 (en) 2013-12-20 2019-03-20 Indivior UK Limited Intranasal naloxone compositions and methods of making and using same
SG11201704797TA (en) 2014-12-23 2017-07-28 Acelrx Pharmaceuticals Inc Systems, devices and methods for dispensing oral transmucosal dosage forms
LT3242676T (en) 2015-01-07 2024-01-25 Tonix Pharma Limited PHARMACEUTICAL FORMS OF OXYTOCIN CONTAINING MAGNESIUM AND THEIR METHODS OF ADMINISTRATION
JP2019507181A (en) 2016-03-04 2019-03-14 チャールストン ラボラトリーズ，インコーポレイテッド Pharmaceutical composition
ES3014046T3 (en) 2016-04-12 2025-04-16 Tonix Pharma Ltd Magnesium-containing oxytocin formulations and methods of use
US10265309B2 (en) * 2016-05-27 2019-04-23 Insys Development Company, Inc. Sublingual opioid formulations containing naloxone
US11331271B2 (en) 2016-05-27 2022-05-17 The Johns Hopkins University Buccal, sublingual and intranasal delivery of fospropofol
IL277801B2 (en) 2018-04-09 2025-06-01 Katana Pharmaceuticals Inc Oxytocin preparations and methods of use
CN109044973A (en) * 2018-11-02 2018-12-21 广东药科大学 A kind of swelling and pain relieving is spraying

Citations (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4495168A (en) * 1983-08-22 1985-01-22 Basf Wyandotte Corporation Aerosol gel
US4704406A (en) * 1985-06-24 1987-11-03 Klinge Pharma Gmbh Sprayable pharmaceutical composition for topical use
US4814161A (en) * 1985-01-16 1989-03-21 Riker Laboratories, Inc. Drug-containing chlorofluorocarbon aerosol propellent formulations
US4863720A (en) * 1986-03-10 1989-09-05 Walter Burghart Pharmaceutical preparation and methods for its production
US4863970A (en) * 1986-11-14 1989-09-05 Theratech, Inc. Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
US5143731A (en) * 1990-08-07 1992-09-01 Mediventures Incorporated Body cavity drug delivery with thermo-irreversible polyoxyalkylene and ionic polysaccharide gels
US5166145A (en) * 1990-09-10 1992-11-24 Alza Corporation Antiemetic therapy
US5240932A (en) * 1990-03-30 1993-08-31 Yasunori Morimoto Percutaneously absorbable compositions of morphine or analogous analgesics of morphine
US5290540A (en) * 1991-05-01 1994-03-01 Henry M. Jackson Foundation For The Advancement Of Military Medicine Method for treating infectious respiratory diseases
US5364616A (en) * 1992-04-15 1994-11-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis
US5502076A (en) * 1994-03-08 1996-03-26 Hoffmann-La Roche Inc. Dispersing agents for use with hydrofluoroalkane propellants
US5602182A (en) * 1995-01-30 1997-02-11 American Home Products Corporation Taste masking pseudoephedrine HCL containing liquids
US5605674A (en) * 1988-12-06 1997-02-25 Riker Laboratories, Inc. Medicinal aerosol formulations
US5607915A (en) * 1992-09-29 1997-03-04 Inhale Therapeutic Systems Pulmonary delivery of active fragments of parathyroid hormone
US5635161A (en) * 1995-06-07 1997-06-03 Abbott Laboratories Aerosol drug formulations containing vegetable oils
US5645856A (en) * 1994-03-16 1997-07-08 R. P. Scherer Corporation Delivery systems for hydrophobic drugs
US5719197A (en) * 1988-03-04 1998-02-17 Noven Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5725841A (en) * 1993-03-17 1998-03-10 Minnesota Mining And Manufacturing Company Aerosol formulation containing an ester-, amide-, or mercaptoester-derived dispersing aid
US5795909A (en) * 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
US5824307A (en) * 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5906811A (en) * 1997-06-27 1999-05-25 Thione International, Inc. Intra-oral antioxidant preparations
US5908611A (en) * 1995-05-05 1999-06-01 The Scripps Research Institute Treatment of viscous mucous-associated diseases
US5955098A (en) * 1996-04-12 1999-09-21 Flemington Pharmaceutical Corp. Buccal non polar spray or capsule
US6143329A (en) * 1996-07-03 2000-11-07 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
US6212227B1 (en) * 1997-12-02 2001-04-03 Conexant Systems, Inc. Constant envelope modulation for splitterless DSL transmission
US6258032B1 (en) * 1997-01-29 2001-07-10 William M. Hammesfahr Method of diagnosis and treatment and related compositions and apparatus
US6271240B1 (en) * 1996-05-06 2001-08-07 David Lew Simon Methods for improved regulation of endogenous dopamine in prolonged treatment of opioid addicted individuals
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US6375975B1 (en) * 1998-12-21 2002-04-23 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary application
US20020102218A1 (en) * 2000-12-01 2002-08-01 Cowan Siu Man L. Stable, aerosolizable suspensions of proteins in ethanol
US6458842B1 (en) * 1994-02-01 2002-10-01 Knoll Aktiengesellschaft Liquid pharmaceutical compositions comprising thyroid hormones
US6512002B2 (en) * 2000-01-12 2003-01-28 Pfizer Inc. Methods of treatment for premature ejaculation in a male
US20030039680A1 (en) * 1997-10-01 2003-02-27 Flemington Pharmaceutical Corporation Buccal, polar and non-polar spray or capsule
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20030077227A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20030191180A1 (en) * 2000-03-09 2003-10-09 Calvin Ross Pharmaceutical compositions
US20040120896A1 (en) * 1997-10-01 2004-06-24 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20040136913A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing sumatriptan
US20040136914A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing ondansetron
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US6816452B1 (en) * 1999-07-14 2004-11-09 Sumitomo Electric Industries, Ltd. Vehicle-to-roadside communication system, roadside communication station, and on-board mobile station
US20040265239A1 (en) * 1997-10-01 2004-12-30 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US7202233B2 (en) * 2000-03-28 2007-04-10 Farmarc Nederland Bv Alprazolam inclusion complexes and pharmaceutical compositions thereof

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE632504A (en) * 1962-05-24
US3304230A (en) * 1963-02-18 1967-02-14 Revlon Liquid aerosol propellant solutions of fatty acid salts of physiologically active amines
SU432703A3 (en) * 1971-08-24 1974-06-15 Фридрих Боссерт, Вульф Фатер, Курт Бауер
SE7812207L (en) * 1977-12-01 1979-06-02 Welsh Nat School Med APPARATUS, PROCEDURE AND MANUFACTURED PRODUCTS FOR USE IN THE ADMINISTRATION OF ANTIHISTAMINES
CA1178889A (en) 1980-08-28 1984-12-04 Kenneth S. Su Intranasal formulation
DE3338978A1 (en) 1982-10-29 1984-05-03 Basf Ag, 6700 Ludwigshafen Verapamil and gallopamil and their physiologically tolerated salts for application onto the mucous membranes of the mouth, of the naso-pharyngeal space and of the rectum for absorption
DE3246081A1 (en) 1982-12-13 1984-06-14 G. Pohl-Boskamp GmbH & Co Chemisch-pharmazeutische Fabrik, 2214 Hohenlockstedt Nitroglycerin spray
IT1169873B (en) 1983-10-21 1987-06-03 Prodotti Formenti Srl PHARMACEUTICAL COMPOSITION WITH SYSTEMIC ANTI-COLINESTERASIC, AGONISTIC-COLINERGIC AND ANTI-MUSCARINIC ACTIVITY
EP0213108A3 (en) 1985-06-26 1987-07-15 Kurt Dr. Burghart Pharmaceutical preparation containing an antihypotonic as the active agent
GB8522453D0 (en) * 1985-09-11 1985-10-16 Lilly Industries Ltd Chewable capsules
DE3544692A1 (en) * 1985-12-18 1987-06-19 Bayer Ag DIHYDROPYRIDINE SPRAY, METHOD FOR THE PRODUCTION THEREOF AND ITS PHARMACEUTICAL USE
US4689233A (en) 1986-01-06 1987-08-25 Siegfried Aktiengesellschaft Coronary therapeutic agent in the form of soft gelatin capsules
JPH0645538B2 (en) * 1987-09-30 1994-06-15 日本化薬株式会社 Nitroglycerin spray
DE3738236A1 (en) 1987-11-11 1989-05-24 Euro Celtique Sa BIT CAPSULE
AU2252388A (en) 1988-05-02 1989-11-29 Zila Pharmaceuticals Compositions and in situ methods for forming films on body tissue
HU199678B (en) * 1988-07-08 1990-03-28 Egyt Gyogyszervegyeszeti Gyar Process for producing aerosols containing nitroglicerol
US5128132A (en) * 1988-11-22 1992-07-07 Parnell Pharmaceuticals, Inc. Eriodictyon compositions and methods for treating internal mucous membranes
US5776434A (en) 1988-12-06 1998-07-07 Riker Laboratories, Inc. Medicinal aerosol formulations
US4935243A (en) * 1988-12-19 1990-06-19 Pharmacaps, Inc. Chewable, edible soft gelatin capsule
US5011678A (en) * 1989-02-01 1991-04-30 California Biotechnology Inc. Composition and method for administration of pharmaceutically active substances
DE3907414A1 (en) 1989-03-08 1990-09-13 Hoechst Ag THE APPLICATION OF INHALED LOOP DIURETICS FOR THE TREATMENT OF ALLERGEN-INDUCED NASAL REACTIONS
DE4000770A1 (en) 1990-01-12 1991-07-18 Reynolds Aluminium Deutschland CONNECTION OF THE JOINT BETWEEN BAR AND POST ON A CARRIER FOR ONE OR ON A FAÇADE WALL
DE4007705C1 (en) * 1990-03-10 1991-09-26 G. Pohl-Boskamp Gmbh & Co. Chemisch-Pharmazeutische Fabrik, 2214 Hohenlockstedt, De
EP0532546B1 (en) * 1990-05-10 1998-03-18 Bechgaard International Research And Development A/S A pharmaceutical preparation containing n-glycofurols and n-ethylene glycols
US5370862A (en) * 1990-06-13 1994-12-06 Schwarz Pharma Ag Pharmaceutical hydrophilic spray containing nitroglycerin for treating angina
DE4026072A1 (en) 1990-08-17 1992-02-20 Sanol Arznei Schwarz Gmbh NITROGLYCER-CONTAINING, HYDROPHILIC, WAESSRING PUMPSPRAY
DE4038203A1 (en) 1990-11-30 1992-06-04 Kali Chemie Pharma Gmbh Pharmaceutical spray-prepn. for admin. of nitrate(s) - esp. for treatment of cardiovascular, disorders, asthma, migraine and colic
US5135753A (en) * 1991-03-12 1992-08-04 Pharmetrix Corporation Method and therapeutic system for smoking cessation
EP0504112A3 (en) 1991-03-14 1993-04-21 Ciba-Geigy Ag Pharmaceutical aerosol formulations
DE4112303A1 (en) 1991-04-15 1992-10-22 Minnesota Mining & Mfg Nitroglycerin, propellant gas-free spray prepn. - stored in container in which the steel parts are made of V4A series steels to inhibit nitroglycerin decomposition
EP0656207B2 (en) * 1991-06-10 2009-07-22 Schering Corporation Non-chlorofluorocarbon aerosol formulations
GB9118830D0 (en) 1991-09-03 1991-10-16 Minnesota Mining & Mfg Medical aerosol formulations
DE4132176C2 (en) 1991-09-27 1997-03-13 Ig Spruehtechnik Gmbh Metered aerosols with isobutane as propellant
US5457100A (en) * 1991-12-02 1995-10-10 Daniel; David G. Method for treatment of recurrent paroxysmal neuropsychiatric
ES2097443T3 (en) 1992-02-20 1997-04-01 Wielligh Johannes Louw Kot Von PRODUCT TO HELP SMOKERS TO ABANDON THE HABIT.
JPH07506839A (en) 1992-12-04 1995-07-27 メイヤー・ファーマシューティカル・ラボラトリース・インコーポレーテッド Sprayable analgesic compositions and methods of use thereof
US5981591A (en) * 1992-12-04 1999-11-09 Mayor Pharmaceutical Laboratories, Inc. Sprayable analgesic composition and method of use
US5362496A (en) * 1993-08-04 1994-11-08 Pharmetrix Corporation Method and therapeutic system for smoking cessation
AU700162B2 (en) * 1994-05-13 1998-12-24 Aradigm Corporation Narcotic containing aerosol formulation
US5519059A (en) * 1994-08-17 1996-05-21 Sawaya; Assad S. Antifungal formulation
US5456677A (en) * 1994-08-22 1995-10-10 Spector; John E. Method for oral spray administration of caffeine
NZ280610A (en) 1994-12-29 1997-08-22 Mcneil Ppc Inc Soft gelatin-like pharmaceutical carrier: gelled polyethylene glycol and dispersed active agent
US5869082A (en) 1996-04-12 1999-02-09 Flemington Pharmaceutical Corp. Buccal, non-polar spray for nitroglycerin
AU2190697A (en) * 1996-04-12 1997-11-07 Flemington Pharmaceutical Corporation Buccal polar spray or capsule
US6071539A (en) * 1996-09-20 2000-06-06 Ethypharm, Sa Effervescent granules and methods for their preparation
ZA9711732B (en) 1996-12-31 1998-12-28 Quadrant Holdings Cambridge Methods and compositions for improvement bioavailability of bioactive agents for mucosal delivery
US20090162300A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing alprazolam
PL347630A1 (en) 1998-11-12 2002-04-22 Frank G Pilkiewicz An inhalation system
GB9908921D0 (en) * 1999-04-19 1999-06-16 Britannia Pharmaceuticals Ltd Spray dispenser for opiod antagonists
DE60231611D1 (en) * 2001-05-24 2009-04-30 Alexza Pharmaceuticals Inc ADMINISTRATION OF OPIOIDES BY INHALATION
WO2002094232A1 (en) 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Delivery of antidepressants through an inhalation route

Patent Citations (82)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4495168A (en) * 1983-08-22 1985-01-22 Basf Wyandotte Corporation Aerosol gel
US4814161A (en) * 1985-01-16 1989-03-21 Riker Laboratories, Inc. Drug-containing chlorofluorocarbon aerosol propellent formulations
US4704406A (en) * 1985-06-24 1987-11-03 Klinge Pharma Gmbh Sprayable pharmaceutical composition for topical use
US4863720A (en) * 1986-03-10 1989-09-05 Walter Burghart Pharmaceutical preparation and methods for its production
US4863970A (en) * 1986-11-14 1989-09-05 Theratech, Inc. Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
US5719197A (en) * 1988-03-04 1998-02-17 Noven Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5605674A (en) * 1988-12-06 1997-02-25 Riker Laboratories, Inc. Medicinal aerosol formulations
US5240932A (en) * 1990-03-30 1993-08-31 Yasunori Morimoto Percutaneously absorbable compositions of morphine or analogous analgesics of morphine
US5143731A (en) * 1990-08-07 1992-09-01 Mediventures Incorporated Body cavity drug delivery with thermo-irreversible polyoxyalkylene and ionic polysaccharide gels
US5166145A (en) * 1990-09-10 1992-11-24 Alza Corporation Antiemetic therapy
US5290540A (en) * 1991-05-01 1994-03-01 Henry M. Jackson Foundation For The Advancement Of Military Medicine Method for treating infectious respiratory diseases
US5824307A (en) * 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
US5364616A (en) * 1992-04-15 1994-11-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis
US5607915A (en) * 1992-09-29 1997-03-04 Inhale Therapeutic Systems Pulmonary delivery of active fragments of parathyroid hormone
US5725841A (en) * 1993-03-17 1998-03-10 Minnesota Mining And Manufacturing Company Aerosol formulation containing an ester-, amide-, or mercaptoester-derived dispersing aid
US6458842B1 (en) * 1994-02-01 2002-10-01 Knoll Aktiengesellschaft Liquid pharmaceutical compositions comprising thyroid hormones
US6706255B2 (en) * 1994-02-01 2004-03-16 Abbott Gmbh & Co., Kg Liquid pharmaceutical compositions comprising thyroid hormones
US5502076A (en) * 1994-03-08 1996-03-26 Hoffmann-La Roche Inc. Dispersing agents for use with hydrofluoroalkane propellants
US5645856A (en) * 1994-03-16 1997-07-08 R. P. Scherer Corporation Delivery systems for hydrophobic drugs
US5602182A (en) * 1995-01-30 1997-02-11 American Home Products Corporation Taste masking pseudoephedrine HCL containing liquids
US5908611A (en) * 1995-05-05 1999-06-01 The Scripps Research Institute Treatment of viscous mucous-associated diseases
US5635161A (en) * 1995-06-07 1997-06-03 Abbott Laboratories Aerosol drug formulations containing vegetable oils
US6299900B1 (en) * 1996-02-19 2001-10-09 Monash University Dermal penetration enhancers and drug delivery systems involving same
US5955098A (en) * 1996-04-12 1999-09-21 Flemington Pharmaceutical Corp. Buccal non polar spray or capsule
US6271240B1 (en) * 1996-05-06 2001-08-07 David Lew Simon Methods for improved regulation of endogenous dopamine in prolonged treatment of opioid addicted individuals
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5795909A (en) * 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
US6143329A (en) * 1996-07-03 2000-11-07 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
US6258032B1 (en) * 1997-01-29 2001-07-10 William M. Hammesfahr Method of diagnosis and treatment and related compositions and apparatus
US5906811A (en) * 1997-06-27 1999-05-25 Thione International, Inc. Intra-oral antioxidant preparations
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20070048229A1 (en) * 1997-10-01 2007-03-01 Novadel Pharma Inc. Buccal, polar and non-polar spray containing atropine
US20060222597A1 (en) * 1997-10-01 2006-10-05 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20030039680A1 (en) * 1997-10-01 2003-02-27 Flemington Pharmaceutical Corporation Buccal, polar and non-polar spray or capsule
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20030077227A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20060216240A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20060216241A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing diazepam
US20030211047A1 (en) * 1997-10-01 2003-11-13 Indena S.P.A. Buccal, polar and non-polar spray or capsule
US6676931B2 (en) * 1997-10-01 2004-01-13 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule
US20060210484A1 (en) * 1997-10-01 2006-09-21 Novadel Pharma Inc. Buccal, polar and non-polar spray containing testosterone
US20040062716A1 (en) * 1997-10-01 2004-04-01 Novadel Pharma Inc. Buccal, polar and non-polar spray of capsule
US20040120895A1 (en) * 1997-10-01 2004-06-24 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20040120896A1 (en) * 1997-10-01 2004-06-24 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20040136913A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing sumatriptan
US20040136914A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing ondansetron
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US20060198790A1 (en) * 1997-10-01 2006-09-07 Dugger Harry A Iii Buccal, polar and non-polar spray containing ondansetron
US20040265239A1 (en) * 1997-10-01 2004-12-30 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20060171896A1 (en) * 1997-10-01 2006-08-03 Dugger Harry A Iii Buccal, polar and non-polar spray containing alprazolam
US20050025717A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20050025713A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20050025716A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20050025715A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20050025714A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20050025712A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20050142069A1 (en) * 1997-10-01 2005-06-30 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US6969508B2 (en) * 1997-10-01 2005-11-29 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US6977070B2 (en) * 1997-10-01 2005-12-20 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050281753A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US6998110B2 (en) * 1997-10-01 2006-02-14 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule
US20060159624A1 (en) * 1997-10-01 2006-07-20 Dugger Harry A Iii Buccal, polar and non-polar spray containing zolpidem
US20060165604A1 (en) * 1997-10-01 2006-07-27 Dugger Harry A Iii Buccal, polar and non-polar spray containing sumatriptan
US6212227B1 (en) * 1997-12-02 2001-04-03 Conexant Systems, Inc. Constant envelope modulation for splitterless DSL transmission
US6375975B1 (en) * 1998-12-21 2002-04-23 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary application
US6816452B1 (en) * 1999-07-14 2004-11-09 Sumitomo Electric Industries, Ltd. Vehicle-to-roadside communication system, roadside communication station, and on-board mobile station
US6512002B2 (en) * 2000-01-12 2003-01-28 Pfizer Inc. Methods of treatment for premature ejaculation in a male
US20030191180A1 (en) * 2000-03-09 2003-10-09 Calvin Ross Pharmaceutical compositions
US7202233B2 (en) * 2000-03-28 2007-04-10 Farmarc Nederland Bv Alprazolam inclusion complexes and pharmaceutical compositions thereof
US20020110524A1 (en) * 2000-12-01 2002-08-15 Cowan Siu Man L. Method for stabilizing biomolecules in liquid formulations
US20020102218A1 (en) * 2000-12-01 2002-08-01 Cowan Siu Man L. Stable, aerosolizable suspensions of proteins in ethanol

Cited By (84)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20030077227A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20040062716A1 (en) * 1997-10-01 2004-04-01 Novadel Pharma Inc. Buccal, polar and non-polar spray of capsule
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US20050025712A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20050025715A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20050025713A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20050025717A1 (en) * 1997-10-01 2005-02-03 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20050142069A1 (en) * 1997-10-01 2005-06-30 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20050281753A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US8236285B2 (en) 1997-10-01 2012-08-07 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20060159624A1 (en) * 1997-10-01 2006-07-20 Dugger Harry A Iii Buccal, polar and non-polar spray containing zolpidem
US20090162298A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing sumatriptan
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20060171896A1 (en) * 1997-10-01 2006-08-03 Dugger Harry A Iii Buccal, polar and non-polar spray containing alprazolam
US20060198790A1 (en) * 1997-10-01 2006-09-07 Dugger Harry A Iii Buccal, polar and non-polar spray containing ondansetron
US20060210484A1 (en) * 1997-10-01 2006-09-21 Novadel Pharma Inc. Buccal, polar and non-polar spray containing testosterone
US20060216240A1 (en) * 1997-10-01 2006-09-28 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US9078816B2 (en) 1997-10-01 2015-07-14 Suda Ltd. Buccal, polar and non-polar spray containing ondansetron
US20090118170A1 (en) * 1997-10-01 2009-05-07 Dugger Iii Harry A Buccal, polar and non-polar spray or capsule
US20100092403A1 (en) * 1997-10-01 2010-04-15 Dugger Iii Harry A Buccal, polar and non-polar spray containing zolpidem
US20060222597A1 (en) * 1997-10-01 2006-10-05 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20100152262A1 (en) * 1997-10-01 2010-06-17 Dugger Iii Harry A Buccal, polar and non-polar spray containing ondansetron
US20060062812A1 (en) * 2003-03-11 2006-03-23 Calvin Ross Novel compositions
WO2004080382A3 (en) * 2003-03-11 2005-03-24 Sirus Pharmaceuticals Ltd Novel compositions containing fentanyl
US20060240050A1 (en) * 2003-07-23 2006-10-26 Douglas Pharmaceuticals Limited Stable clozapine suspension formulation
US8057811B2 (en) 2003-07-23 2011-11-15 Douglas Pharmaceuticals Limited Stable clozapine suspension formulation
US7658945B2 (en) 2004-02-17 2010-02-09 Transcept Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US7682628B2 (en) 2004-02-17 2010-03-23 Transcept Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20050226925A1 (en) * 2004-02-17 2005-10-13 Transoral Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20080008753A1 (en) * 2004-02-17 2008-01-10 Singh Nikhilesh N Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
US20060002989A1 (en) * 2004-06-10 2006-01-05 Ahmed Salah U Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same
EP2767163A1 (en) 2005-02-17 2014-08-20 Abbott Laboratories Transmucosal administration of drug compositions for treating and preventing disorders in animals
WO2006105205A1 (en) * 2005-03-29 2006-10-05 University Of Kentucky Research Foundation Sublingual spray for the treatment of pain
US20060276501A1 (en) * 2005-05-25 2006-12-07 Transoral Pharmaceuticals, Inc. Solid compositions for treating middle-of-the-night insomnia
US20070123562A1 (en) * 2005-05-25 2007-05-31 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the-night insomnia
US20070225322A1 (en) * 2005-05-25 2007-09-27 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the night insomnia
US20100249178A1 (en) * 2005-05-25 2010-09-30 Nikhilesh Singh Compositions and methods for treating middle-of-the-night insomnia
US20100249177A1 (en) * 2005-05-25 2010-09-30 Singh Nikhilesh N Compositions and methods for treating middle-of-the-night insomnia
US20110039881A1 (en) * 2005-05-25 2011-02-17 Singh Nikhilesh N Compositions and methods for treating middle-of-the-night insomnia
US20080057119A1 (en) * 2005-05-25 2008-03-06 Singh Nikhilesh N Compositions and methods for treating middle-of-the night insomnia
US8252809B2 (en) 2005-05-25 2012-08-28 Transcept Pharmaceuticals, Inc. Compositions for treating insomnia
US8242131B2 (en) 2005-05-25 2012-08-14 Transcept Pharmaceuticals, Inc. Methods of treating middle-of-the-night insomnia
US20070287740A1 (en) * 2005-05-25 2007-12-13 Transcept Pharmaceuticals, Inc. Compositions and methods of treating middle-of-the night insomnia
EP2801358A3 (en) * 2006-05-08 2015-03-04 Arturo Solis Herrera The use of nicotine for diminishing pain in renal region in humans
US10799466B2 (en) * 2006-09-20 2020-10-13 The Board Of Regents Of The University Of Texas System Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief
US10357464B2 (en) * 2006-09-20 2019-07-23 The Board Of Regents Of The University Of Texas System Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief
US20080171089A1 (en) * 2006-12-22 2008-07-17 Blondino Frank E Stable anti-nausea oral spray formulations and methods
US20080280947A1 (en) * 2007-05-10 2008-11-13 Blondino Frank E Anti-insomnia compositions and methods
US20110040266A1 (en) * 2007-05-10 2011-02-17 Blondino Frank E Anti-insomnia compositions and methods
US10420720B2 (en) * 2008-01-22 2019-09-24 The Board Of Regents Of The University Of Texas System Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief
EP2436383A4 (en) * 2009-05-29 2014-02-26 Morishita Jintan Co ORAL MEDICINAL COMPOSITION AND ORAL MEDICINAL CAPSULE CONTAINING ENCAPSULATED COMPOSITION INSIDE
US20120093925A1 (en) * 2009-05-29 2012-04-19 Morishita Jintan Co., Ltd. Oral medicinal composition and oral medicinal capsule having the composition encapsulated therein
KR101704081B1 (en) 2009-05-29 2017-02-07 모리시타 진탄 가부시키가이샤 Oral medicinal composition and oral medicinal capsule having the composition encapsulated therein
KR20120028349A (en) * 2009-05-29 2012-03-22 모리시타 진탄 가부시키가이샤 Oral medicinal composition and oral medicinal capsule having the composition encapsulated therein
WO2011036521A2 (en) 2009-09-25 2011-03-31 Dr. Reddy's Laboratories Limited Formulations comprising triptan compounds
US9211282B2 (en) 2009-09-25 2015-12-15 Dr. Reddy's Laboratories Ltd. Formulations comprising triptan compounds
US12090139B2 (en) 2009-09-25 2024-09-17 Tonix Medicines, Inc. Formulations comprising triptan compounds
US11337962B2 (en) 2009-09-25 2022-05-24 Upsher-Smith Laboratories, Llc Formulations comprising triptan compounds
US9610280B2 (en) 2009-09-25 2017-04-04 Dr. Reddy's Laboratories Limited Formulations comprising triptan compounds
US20110077281A1 (en) * 2009-09-25 2011-03-31 Dr. Reddy's Laboratories Limited Formulations Comprising Triptain Compounds
US9974770B2 (en) 2009-09-25 2018-05-22 Dr. Reddy's Laboratories Ltd. Formulations comprising triptan compounds
US10603305B2 (en) 2009-09-25 2020-03-31 Upsher-Smith Laboratories, Llc Formulations comprising triptan compounds
WO2014033680A1 (en) * 2012-08-31 2014-03-06 Assistance Publique - Hopitaux De Paris Gelling formulation containing ketamine
US10307385B2 (en) 2012-08-31 2019-06-04 Assistance Publique-Hopitaux De Paris Gelling formulation containing ketamine
US10195153B2 (en) 2013-08-12 2019-02-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10639281B2 (en) 2013-08-12 2020-05-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10792254B2 (en) 2013-12-17 2020-10-06 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US11975096B2 (en) 2014-07-08 2024-05-07 Hikma Pharmaceuticals Usa Inc. Liquid naloxone spray
US9707184B2 (en) 2014-07-17 2017-07-18 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US10959958B2 (en) 2014-10-20 2021-03-30 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form
CN105193774A (en) * 2015-09-21 2015-12-30 山东新时代药业有限公司 Sevoflurane inhalant
CN113350277A (en) * 2021-06-30 2021-09-07 广东科伦药业有限公司 Mesalazine gargle for treating chemotherapy oral mucositis and preparation method thereof

Also Published As

Publication number Publication date
US20040120896A1 (en) 2004-06-24
WO2004043428A2 (en) 2004-05-27
US6969508B2 (en) 2005-11-29
JP2006505611A (en) 2006-02-16
EP1539107A2 (en) 2005-06-15
US20090124554A1 (en) 2009-05-14
WO2004043428A3 (en) 2004-10-21
CA2497268A1 (en) 2004-05-27
US20120252846A1 (en) 2012-10-04
AU2003296899A1 (en) 2004-06-03
NZ539284A (en) 2007-07-27

Similar Documents

Publication Publication Date Title
US6969508B2 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20060165604A1 (en) Buccal, polar and non-polar spray containing sumatriptan
US9078816B2 (en) Buccal, polar and non-polar spray containing ondansetron
US6998110B2 (en) Buccal, polar and non-polar spray or capsule
US20030095927A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030095926A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20050025714A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
EP1539097A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20050287075A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating pain
EP1444976A1 (en) Buccal, polar and non-polar spray or capsule

Legal Events

Date Code Title Description
AS Assignment

Owner name: NOVADEL PHARMA INC., NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DUGGER, HARRY A., III;REEL/FRAME:013490/0992

Effective date: 20021016

AS Assignment

Owner name: PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT

Free format text: SECURITY AGREEMENT;ASSIGNOR:NOVADEL PHARMA INC.;REEL/FRAME:021029/0574

Effective date: 20080506

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: NOVADEL PHARMA INC., NEW JERSEY

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:PROQUEST INVESTMENTS III, L.P. AS COLLATERAL AGENT;REEL/FRAME:024915/0277

Effective date: 20100830