CN119112808A - Captopril microtablet and preparation method thereof - Google Patents
Captopril microtablet and preparation method thereof Download PDFInfo
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- CN119112808A CN119112808A CN202411099969.9A CN202411099969A CN119112808A CN 119112808 A CN119112808 A CN 119112808A CN 202411099969 A CN202411099969 A CN 202411099969A CN 119112808 A CN119112808 A CN 119112808A
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- captopril
- microtablet
- preparation
- microplate
- microtablets
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- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 title claims abstract description 33
- 229960000830 captopril Drugs 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title abstract description 27
- 238000005469 granulation Methods 0.000 claims abstract description 8
- 230000003179 granulation Effects 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- 239000007921 spray Substances 0.000 claims abstract description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 8
- 235000021355 Stearic acid Nutrition 0.000 claims description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 8
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 8
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 8
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 8
- 239000008117 stearic acid Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- 239000000314 lubricant Substances 0.000 claims description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 238000005550 wet granulation Methods 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 238000007908 dry granulation Methods 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 235000012222 talc Nutrition 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- 229920002261 Corn starch Polymers 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 229940061587 calcium behenate Drugs 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- SMBKCSPGKDEPFO-UHFFFAOYSA-L calcium;docosanoate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCCCCCC([O-])=O SMBKCSPGKDEPFO-UHFFFAOYSA-L 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 239000008120 corn starch Substances 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229940014259 gelatin Drugs 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 15
- 206010020772 Hypertension Diseases 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000002503 metabolic effect Effects 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 23
- 238000005507 spraying Methods 0.000 description 13
- 238000002156 mixing Methods 0.000 description 11
- 239000000853 adhesive Substances 0.000 description 10
- 230000001070 adhesive effect Effects 0.000 description 10
- 239000008187 granular material Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 4
- 230000006399 behavior Effects 0.000 description 3
- 230000035487 diastolic blood pressure Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000005453 pelletization Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000035488 systolic blood pressure Effects 0.000 description 3
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 238000000889 atomisation Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229950003442 methoprene Drugs 0.000 description 1
- 229930002897 methoprene Natural products 0.000 description 1
- 239000008185 minitablet Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 229940051841 polyoxyethylene ether Drugs 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 230000035485 pulse pressure Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明公开了一种治疗高血压类疾病的卡托普利微片制剂，以及一种制备卡托普利微片的方法，通过顶喷流化床制粒等制备方法，制备得到了可压性良好的卡托普利微片，本发明的卡托普利微片可以以小剂量多次给药，尤其是对于个体代谢差异性大的人群，如老年人和幼儿，可以计数服用，做到精准给药，并且对于服用常规制剂有困难的人群，可以提高服药的顺应性。The invention discloses a captopril microtablet preparation for treating hypertension-related diseases and a method for preparing the captopril microtablet. Captopril microtablets with good compressibility are prepared by top-spray fluidized bed granulation and other preparation methods. The captopril microtablets of the invention can be administered multiple times in small doses, especially for people with large individual metabolic differences, such as the elderly and infants, the doses can be counted and accurately administered, and the compliance of the medication can be improved for people who have difficulty taking conventional preparations.
Description
The application relates to a Chinese patent application with the application date of 2016, 6 and 20, the application number of 201610443201.8 and the name of 'captopril microchip and a preparation method thereof'.
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a captopril microchip and a method for preparing the captopril microchip.
Background
Hypertension (hypertension) refers to a clinical syndrome characterized by an increase in systemic arterial blood pressure (systolic and/or diastolic blood pressure) (systolic pressure. Gtoreq.140 mmHg, diastolic pressure. Gtoreq.90 mmHg), accompanied by functional or organic impairment of organs such as heart, brain, kidneys, etc. Hypertension is the most common chronic disease and is also the most important risk factor for cardiovascular and cerebrovascular diseases. The blood pressure of normal people fluctuates within a certain range along with the internal and external environment changes. In the whole population, the blood pressure level gradually increases with age to make the systolic blood pressure more obvious, but the diastolic blood pressure shows a decreasing trend after 50 years of age, and the pulse pressure also increases. The blood pressure value and risk factor evaluation are the main basis for diagnosing and formulating a hypertension treatment scheme, targets of hypertension management of different patients are different, and doctors face patients on the basis of reference standards, judge the most suitable blood pressure range of the patients according to specific conditions, and adopt targeted treatment measures.
At present, a series of medicines for hypertension, namely captopril (captopril, methoprene and kebotong), are developed at home and abroad, are first-generation orally effective Angiotensin Converting Enzyme Inhibitors (ACEI), and since the advent of 1997, the efficacy of antihypertensive and congestive heart failure treatment of the same has been acknowledged. Captopril has a remarkable antihypertensive effect on various types of hypertension and can improve the heart function of patients suffering from congestive heart failure. Clinically, the traditional Chinese medicine composition is used for various types of hypertension, and is particularly effective for severe hypertension which is ineffective in conventional therapy. Can also be used for treating intractable chronic heart failure.
The micro tablet is a micro tablet with the diameter of 1-3 mm formed by stamping by a special tablet press, the micro tablet belongs to a dose dispersion preparation, the micro tablet is uniformly dispersed in the gastrointestinal tract after being orally taken by a patient, the irritation to the gastrointestinal tract is reduced, the gastrointestinal transportation and absorption of the medicine are less influenced by the gastric emptying rate, thus the individual variability is small, the medicine release behavior of the micro tablet is the sum of the medicine release behaviors of a plurality of small units forming one dose, and the medicine release behavior of the whole preparation cannot be seriously influenced by the defects of the preparation process of the individual small units after the oral administration. For people with large individual differences in drug metabolism, such as the elderly and infants, or for drugs with dosages needing to be adjusted at any time, the microchip is a relatively ideal administration form, and patients can count and take the microchip according to an individual administration scheme, so that the metering is more accurate. The microtablets are more regular in shape and more uniform in size than other multicell dosage forms. Because the microchip is pressed by a fixed die, the tablet has the characteristics of common tablets, the tablet weight and the size are accurate and controllable, the reproducibility of production is good, and each microchip unit has the same size, weight and medicine content.
At present, only two common dosage forms of a tablet and a dripping pill are clinically used at home and abroad, and the existing captopril dosage form can not meet the requirement of individual medication and can achieve accurate medication when the dosage is required to be administered in a small dosage, such as when the dosage is required to be administered by children or when the dosage is required to be adjusted at any time, such as when the dosage is required to be administered by the old people. In addition, when the existing pharmaceutical dosage forms are taken, the compliance of taking medicines is poor for special people, especially children, due to the overlarge volume of the dosage forms.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a captopril microchip preparation. The captopril micro-tablet can be repeatedly dosed in small dosage through a special granulating formula and a preparation process, especially for people with large individual metabolic variability, such as the elderly and infants, can be accurately dosed, various side effects caused by inaccurate dosing can be reduced while accurate dosing is achieved, and the compliance of dosing can be improved for people with difficulty in dosing conventional preparations.
In order to achieve the aim of the invention, the invention provides a captopril microchip preparation, which comprises the following prescription raw materials and the dosage ratio:
captopril 0.4-0.8
7.0 To 8.0 portions of diluent
0.2 To 0.6 of adhesive
0.04-0.2 Parts of lubricant.
The captopril microchip preparation disclosed by the invention is characterized in that the raw materials in the microchip and the dosage ratio of the raw materials are preferably as follows:
Captopril 0.6
Diluent 7.6
Adhesive 0.4
Lubricant 0.08.
Wherein the diluent is one or more selected from starch, pregelatinized starch, dextrin, microcrystalline cellulose and lactose. The adhesive is one or more selected from HPMC, povidone, gelatin, poloxamer, microcrystalline cellulose and polyvinylpyrrolidone. The lubricant is one or more selected from magnesium stearate, talcum powder, corn starch, stearic acid, calcium stearate, talcum and calcium behenate.
The excipients included in the microchip preparation of the present invention are not limited to the types listed in the summary and examples, and may also include other pharmaceutical excipients, provided that the compression molding of the microchip is not affected. For example, surfactants may be included, which may be selected from sorbitol, mannitol, sodium lauryl sulfate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene, and the like.
The spatial shape of the flits can in principle be chosen as desired. The microchip of the present invention preferably has a cylindrical, oval or spherical spatial shape. Preferably, the height and the diameter of the cylindrical shape can be 1-4 mm, and the height and the diameter can be arbitrarily selected according to the needs, such as the height and the diameter can be 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm and the like respectively.
In the microchip preparation of the present invention, the surface of the microchip may also be coated by a known method. The active substance captopril can be released in an aqueous medium, for example, by applying at least one coating layer, in a controlled (generally delayed) manner. Suitable controlled release coatings contain water insoluble waxes or polymers, preferably ethylcellulose.
The microchip preparation of the present invention may also contain a coating which may be dissolved, for example, in a pH dependent manner, ensuring that the microchip preparation does not dissolve through the stomach until it reaches the intestine.
The captopril micro-tablet preparation can be filled into a capsule to prepare an oral preparation in the form of the capsule, and the capsule contains a certain number of micro-tablets capable of controllably releasing the medicine, and the number of the micro-tablets is determined according to single release time and the amount of the medicine to be released. The number of microtablets in the capsule is preferably sufficient for a once or twice daily dose. The advantage of using this dosage form is that the dose of the active ingredient is subdivided among many directly countable microtablets, but since the dose is already established in the capsule, the patient does not have to count cumbersome anymore.
The microchip formulations of the present invention may be used alone or in combination with a specialized drug delivery device, such as a drug dispensing device, to provide for more convenient and accurate administration.
Another object of the present invention is to provide a method for preparing captopril minitablets, which can be prepared by fluidized bed top-spray granulation, wet granulation, dry granulation or fluidized bed bottom-spray granulation.
When the top-spraying granulation process is adopted, the preparation method comprises the steps of adding captopril and an adhesive into purified water, stirring until a clear transparent solution is formed and used as a granulating adhesive solution for standby, premixing a diluent, putting the diluent into a fluidized bed top-spraying pot body, starting a fluidized bed blast, adjusting atomization pressure and air inlet temperature, spraying the adhesive solution for top-spraying granulation, taking out the granules after the adhesive solution is sprayed, carrying out dry granulation, uniformly mixing the obtained dry granules with a prescribed amount of lubricant, and transferring the mixed material to a high-speed rotary tablet press for tabletting to obtain finished tablets.
Or adopting wet granulation process, the preparation method comprises placing captopril, diluent and binder in a pan of wet granulator, spraying purified water after mixing, wet granulating, drying, granulating, mixing with lubricant, and tabletting.
Detailed Description
Example 1:
| Name of the name | Dosage of |
| Captopril | 0.6mg |
| Microcrystalline cellulose 102 | 2.4mg |
| Lactose Flowlac100 | 5.2mg |
| HPMC E3 | 0.4mg |
| Stearic acid | 0.08mg |
The preparation process comprises adding captopril and HPMC E3 into purified water, stirring to form clear transparent solution as granulating binder solution, premixing microcrystalline cellulose 102 and lactose Flowlac, placing into a fluidized bed top-spraying pan, opening fluidized bed air blast, adjusting atomization pressure and air inlet temperature, spraying binder solution for top-spraying granulation, taking out the granule after the binder solution is sprayed, drying, mixing the obtained dry granule with stearic acid of prescribed amount, and transferring the mixture to a high-speed rotary tablet press for tabletting to obtain final product captopril micro tablet.
Example 2:
The preparation process comprises the steps of placing captopril, lactose Flowlac and HPMC E3 in a pan of a wet granulator, starting paddles for primary mixing for 10min, starting paddles for spraying purified water for wet granulation after mixing, continuously granulating for 5min after spraying purified water, wet granulating the obtained wet granules, drying the wet granules in a fluidized bed, drying the dried granules, uniformly mixing the dried granules with the prescription amount of stearic acid, and transferring the mixed materials to a high-speed rotary tabletting machine for tabletting to obtain the finished captopril micro-tablets.
Example 3:
The preparation process comprises the steps of uniformly mixing captopril, microcrystalline cellulose 102 and HPMC E3, adding the mixed material into a dry granulator to obtain proper dry-method granules, uniformly mixing the granules with stearic acid, and transferring the mixed material to a high-speed rotary tablet press for tabletting to obtain the finished tablet.
Example 4
The preparation process includes adding captopril and povidone K30 into purified water, stirring to form clear transparent solution as pelletizing adhesive solution, pre-mixing microcrystalline cellulose 102, adding the pre-gelatinized starch into a fluidized bed top spraying pot, starting the fluidized bed to blow air, regulating atomizing pressure and air intake temperature, spraying adhesive solution for top spraying pelletizing, taking out the pellets after the adhesive solution is sprayed, drying and pelletizing, mixing the obtained dry pellets with the prescribed amount of stearic acid, and transferring the mixed material to a high-speed rotary tablet press for tabletting to obtain the finished microchip preparation.
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411099969.9A CN119112808A (en) | 2016-06-20 | 2016-06-20 | Captopril microtablet and preparation method thereof |
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| CN202411099969.9A CN119112808A (en) | 2016-06-20 | 2016-06-20 | Captopril microtablet and preparation method thereof |
| CN201610443201.8A CN107519137A (en) | 2016-06-20 | 2016-06-20 | A kind of captopril microchip and preparation method thereof |
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| US4666705A (en) * | 1985-06-03 | 1987-05-19 | E. R. Squibb & Sons, Inc. | Controlled release formulation |
| US5298497A (en) * | 1990-05-15 | 1994-03-29 | E. R. Squibb & Sons, Inc. | Method for preventing onset of hypertension employing a cholesterol lowering drug |
| CN1251673C (en) * | 2003-12-10 | 2006-04-19 | 杭州民生药业集团有限公司 | Controlled release preparation of captopril and its preparation process |
| CN104490754A (en) * | 2014-12-05 | 2015-04-08 | 海南卫康制药(潜山)有限公司 | Lyophilized tablet prepared from captopril composition and preparation method thereof |
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