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CN113274357A - Amoxicillin medicine and preparation method thereof - Google Patents

Amoxicillin medicine and preparation method thereof Download PDF

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Publication number
CN113274357A
CN113274357A CN202110589298.4A CN202110589298A CN113274357A CN 113274357 A CN113274357 A CN 113274357A CN 202110589298 A CN202110589298 A CN 202110589298A CN 113274357 A CN113274357 A CN 113274357A
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amoxicillin
dry
preparation
sucrose
filler
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CN113274357B (en
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王健松
王玮
邢盛
黄海文
邓雪晴
李翠芬
林大富
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Guangzhou Baiyunshan Pharmaceutical Holdings Co ltd Baiyunshan Pharmaceutical General Factory
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Guangzhou Baiyunshan Pharmaceutical Holdings Co ltd Baiyunshan Pharmaceutical General Factory
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    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
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    • A—HUMAN NECESSITIES
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    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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
    • A61P31/04—Antibacterial agents

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Abstract

The invention belongs to the technical field of medicines, and discloses an amoxicillin medicine and a preparation method thereof. The amoxicillin medicine comprises the following components: amoxicillin, filler and binder; the adhesive is crospovidone. The invention adopts the crospovidone as the adhesive and the dry granulation technology, and the yield of the prepared amoxicillin medicine is high and can reach more than 70 percent; can be quickly dissolved in water, a solution with pH1.2, pH4.0 and pH6.8, and the dissolution rate is over 85 percent within 15 minutes; and the product stability is good. The preparation method has simple process, and does not need secondary granulation.

Description

Amoxicillin medicine and preparation method thereof
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an amoxicillin medicine and a preparation method thereof.
Background
Amoxicillin is a broad-spectrum antibiotic, exerts a bactericidal effect by inhibiting the synthesis of bacterial cell walls, can make bacteria quickly become spheroids to be dissolved and broken, has strong and quick killing effect on gram-negative bacteria and gram-positive bacteria, and also has killing effect on leptospira. The amoxicillin has good effect on the treatment of respiratory system, urinary system and digestive system infection. The amoxicillin oral dosage form comprises tablets, capsules, granules, dispersible tablets and the like, wherein amoxicillin granules are commonly used in clinic.
However, amoxicillin has poor solubility, is slightly soluble in water and is insoluble in ethanol, so that the prepared amoxicillin granules have poor dissolution and become a key factor for limiting the in vivo absorption. The amoxicillin granules are used by children and old people, and the amoxicillin granules hope to take effect quickly after being taken, so that the amoxicillin granules can be quickly dissolved out in vitro (the dissolution rate in 500 ml of dissolution medium is over 85 percent within 15 minutes), and the amoxicillin granules have important clinical significance for quick in vivo effect. In addition, amoxicillin is sensitive to humidity and heat (the temperature is higher than 40 ℃), has poor stability under high temperature and high humidity, obviously increases impurities, and is easy to cause anaphylactic reaction. Such as wet granulation, drying processes also result in a substantial increase in impurities.
Researches show that the amoxicillin granules are prepared by wet granulation, and the particle size of amoxicillin is controlled, so that the product can be quickly dissolved out in a plurality of media, but the stability of the finished product is poor, and the increase of impurities in the lofting process is obvious; if the particle size of the finished product (amoxicillin medicine) is only controlled, the aim of quick dissolution cannot be achieved. The dry granulation technology is adopted, drying is not needed, and the influence on the medicines which are sensitive to damp and heat, such as cephalosporins and amoxicillin, is small; however, the granules obtained by conventional dry pressing are often in the form of flakes or blocks, have irregular corners, are difficult to sieve during granulation, and have a significantly reduced yield (finished product quality/material charge) 100%), often less than 70%. Therefore, secondary tabletting and secondary size stabilization are often needed, and secondary dry pressing can cause obvious increase of impurities in the lofting process and increase of production procedures, so that the application in actual production is less.
Therefore, a need exists for amoxicillin granules with high yield.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art described above. Therefore, the invention provides an amoxicillin medicine, which has high yield, and can reach more than 70 percent, even 84 percent.
The invention conception is as follows: the invention takes the crospovidone as a dry adhesive for the first time, and prepares the amoxicillin medicament by a dry preparation process. The process can obviously improve the yield, and can solve the problems of complicated working procedures in dry granulation and increase of unstable impurities caused by wet granulation in the prior art.
The invention provides an amoxicillin medicament in a first aspect.
Specifically, the amoxicillin medicine comprises the following components: amoxicillin, filler and binder; the adhesive is crospovidone.
The adhesive is crospovidone. The method has the advantages that the polyvinylpolypyrrolidone is used as the adhesive, the yield can be effectively improved through a dry preparation process, the preparation process is simplified, secondary granulation is not needed, the types of auxiliary materials are few, the prescription composition is simple, and the economical efficiency is better on the premise that the product quality is safe and effective. Meanwhile, the crospovidone is a water-insoluble tablet disintegrating agent or dissolving agent, the maximum water absorption capacity of the crospovidone is close to 60% after the crospovidone meets water, high capillary activity and excellent hydration capability can be rapidly expressed, almost no gel tendency exists, and the amoxicillin medicine prepared by matching the crospovidone with the filling agent can obtain higher dissolving rate.
Preferably, the mass of the adhesive accounts for 2-5% of the mass of the amoxicillin medicine. By controlling the dosage of the adhesive, the dissolution rate and the stability of the amoxicillin medicine can be further improved.
Preferably, the particle size distribution of the amoxicillin is D10: 2.5-10.0 μm, D50: 7.0-35.0 μm, D90: 12.0-55.0 μm; the particle size distribution of the filler is D10: 3.0-9.0 μm, D50: 20.0-70.0 μm, D90: 90.0-230.0 μm.
The particle sizes of amoxicillin and the filler are controlled, so that the dissolution speed can be improved; meanwhile, the powder properties can be improved by mixing the amoxicillin and the filler within a proper particle size range, so that the mixed powder of the amoxicillin and the filler is beneficial to dry pressing and molding, and the yield is further improved.
Preferably, the specification of the amoxicillin in the amoxicillin medicine is 0.1g-0.5 g.
Preferably, the particle size distribution of the amoxicillin is D10: 2.5-7.0 μm, D50: 7.0-20.0 μm, D90: 12.0-40.0 μm.
Preferably, the filler is selected from at least one of sucrose, starch, dextrin or microcrystalline cellulose.
Preferably, the particle size distribution of the filler is D10: 4.0-9.0 μm, D50: 30.0-70.0 μm, D90: 130.0-220.0 μm; more preferably, the particle size distribution of the filler is D10: 5.0-8.0 μm, D50: 40.0-60.0 μm, D90: 150.0-200.0 μm.
Preferably, the amoxicillin medicine comprises the following components in percentage by mass: 10-20% of amoxicillin, 75-88% of filling agent and 2-5% of adhesive.
Further preferably, the amoxicillin drug comprises the following components in percentage by mass: 10-15% of amoxicillin, 80-88% of filling agent and 2-5% of adhesive.
Preferably, the amoxicillin medicine also comprises auxiliary materials. The auxiliary materials are selected from one or more of wetting agents, lubricating agents, disintegrating agents, coloring agents or essences.
The invention also provides a preparation method of the amoxicillin medicine.
Specifically, the preparation method comprises the following steps:
weighing amoxicillin, a filling agent and a binding agent, mixing, dry-pressing and granulating to obtain the amoxicillin medicine.
Preferably, the pressure of the dry pressure is 60-90bar, and the sample feeding speed in the dry pressure process is 50-80 rpm. Further preferably, the pressure of the dry pressure is 70-90bar, the sample feeding speed in the dry pressure process is 60-75rpm,
preferably, screw sample feeding is used in the dry pressing process.
The influence of pressure and feeding speed on powder compression molding in the dry pressing process is large. Researches show that more fine powder is generated due to too low pressure, the yield is influenced, and the heat generated by materials in the pressing process is generated due to too high pressure, so that the impurity growth in the lofting process is obvious; the feeding amount is lower than the amount of materials required by dry pressing due to too low feeding speed, the materials are difficult to compact after being pressed, and the yield is influenced due to more fine powder; too high feeding speed can lead to a large amount of materials to be pressed to be piled up at the front end of the pressing wheel, continuous friction heating is carried out, and impurities are obviously increased.
Preferably, the diameter of the granulating hole in the granulating process is 0.8 mm.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention adopts the crospovidone as the adhesive and combines with the dry granulation technology, and the yield of the prepared amoxicillin medicine is high and can reach more than 70 percent, even 84 percent; and can be quickly dissolved in water, pH1.2, pH4.0, pH6.8 solution, and the dissolution rate is over 85% in 15 min.
(2) The preparation method provided by the invention has the advantages of simple process, no need of secondary granulation, less auxiliary material types and low production cost.
Detailed Description
In order to make the technical solutions of the present invention more apparent to those skilled in the art, the following examples are given for illustration. It should be noted that the following examples are not intended to limit the scope of the claimed invention.
The starting materials, reagents or apparatuses used in the following examples are conventionally commercially available or can be obtained by conventionally known methods, unless otherwise specified.
Example 1
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000031
Figure BDA0003088810130000041
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting the dry pressure of 60bar and the spiral feeding speed of 50rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 2
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000042
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D107.0 mu m, D5020.0 mu m and D9040.0 mu m and sucrose with the particle sizes of D106.0 mu m, D5050.0 mu m and D90170.0 mu m, uniformly mixing with other auxiliary materials, setting the dry pressure to 90bar and the screw feeding speed to 70rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 3
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000043
Figure BDA0003088810130000051
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D104.5 mu m, D5014.0 mu m and D9030.0 mu m and sucrose with the particle sizes of D109.0 mu m, D5070.0 mu m and D90220.0 mu m, uniformly mixing with other auxiliary materials, setting a dry pressure of 80bar and a spiral feeding speed of 80rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 4
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000052
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D105.5 mu m, D5015.0 mu m and D9022.0 mu m and sucrose with the particle sizes of D108.0 mu m, D5055.0 mu m and D90200.0 mu m, uniformly mixing with other auxiliary materials, setting a dry pressure of 80bar and a spiral feeding speed of 80rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 5
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000053
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting a dry pressure of 80bar and a spiral feeding speed of 80rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 6
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000061
the preparation method comprises the following steps:
unprocessed amoxicillin raw materials, crushing and sieving sucrose to obtain amoxicillin with the particle sizes of D1012.0 μm, D5040.0 μm and D9060.0 μm, wherein the particle sizes of the sucrose are D104.0 μm, D5030.0 μm and D90130.0 μm, the amoxicillin raw materials and the rest auxiliary materials are uniformly mixed, the dry pressure is set to be 80bar, the spiral feeding speed is set to be 80rpm, the powder is pressed into a sheet shape by a dry press, the powder is granulated by a 0.8mm screen, particles with 14 holes/25.4 mm to 65 holes/25.4 mm are collected, essence is added, the mixture is uniformly mixed, and the mixture is subpackaged into 1000 bags, thus obtaining the amoxicillin tablet.
Example 7
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000062
the preparation method comprises the following steps:
pulverizing and sieving amoxicillin raw material, untreated sucrose, uniformly mixing the obtained amoxicillin with the particle sizes of D102.5 μm, D507.0 μm and D9012.0 μm, the sucrose with the particle sizes of D1010.0 μm, D5080.0 μm and D90240.0 μm with other auxiliary materials, setting dry pressure of 70bar and screw feeding speed of 80rpm, pressing the powder into tablets by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 8
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000071
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting the dry pressure of 100bar and the spiral feeding speed of 80rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 9
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000072
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting a dry pressure of 50bar and a spiral feeding speed of 50rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 10
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000081
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting the dry pressure of 80bar and the screw feeding speed of 90rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Example 11
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000082
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting a dry pressure of 80bar and a spiral feeding speed of 40rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm granulator, collecting 14-hole/25.4-65-hole/25.4 mm granules, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Comparative example 1
Comparative example 1 differs from example 1 in that: adopts copovidone to replace crospovidone.
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000083
Figure BDA0003088810130000091
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting a dry pressure of 80bar and a spiral feeding speed of 70rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Comparative example 2
Comparative example 2 differs from example 1 in that: low-substituted hydroxypropyl cellulose is adopted to replace crospovidone.
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000092
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting dry pressure of 70bar and screw feeding speed of 50rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Comparative example 3
Comparative example 3 differs from example 1 in that: hydroxypropyl methylcellulose is adopted to replace crospovidone.
An amoxicillin drug comprises the following components:
Figure BDA0003088810130000093
Figure BDA0003088810130000101
the preparation method comprises the following steps:
respectively crushing and sieving an amoxicillin raw material and sucrose to obtain amoxicillin with the particle sizes of D102.5 mu m, D507.0 mu m and D9012.0 mu m and sucrose with the particle sizes of D104.0 mu m, D5030.0 mu m and D90130.0 mu m, uniformly mixing with other auxiliary materials, setting dry pressure of 70bar and screw feeding speed of 80rpm, pressing the powder into a sheet by a dry press, granulating by a 0.8mm screen, collecting 14 holes/25.4 mm to 65 holes/25.4 mm particles, adding essence, uniformly mixing, and subpackaging into 1000 bags to obtain the amoxicillin tablet.
Product effectiveness testing
(1) The yields of examples 1 to 11 and comparative examples 1 to 3 were measured, respectively.
The yield is calculated according to the formula (finished product quality/material input) 100%, and the yield of each example and comparative example is shown in table 1:
table 1: comparison of yields (%)
Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7
83.8 84.0 83.5 70.6 78.6 72.9 75.3
Example 8 Example 9 Example 10 Example 11 Comparative example 1 Comparative example 2 Comparative example 3
76.0 71.3 78.7 70.6 50.3 62.1 65.3
The results show that the yield of the amoxicillin medicine prepared in the examples is above 70%, which is higher than that of the comparative example, the yield of the medicine can be improved by adopting the crospovidone as the binder, and when the amoxicillin medicine is replaced by other binders, the yield is below 70%.
(2) Dissolution rates of examples 1 to 11 and comparative examples 1 to 3 were measured, respectively
The amoxicillin drugs prepared in examples 1-11 and comparative examples 1-3 were placed in water, four media of pH1.2, pH4.0 and pH6.8, respectively, and dissolution within 15min was measured.
Table 2: dissolution (%) -of examples and comparative examples
Figure BDA0003088810130000102
Figure BDA0003088810130000111
Note: "√" indicates a dissolution rate of more than 85% in 15min, and "×" indicates a dissolution rate of less than 85% in 15 min.
The results show that the amoxicillin medicine prepared in the examples has dissolution rate of more than 85% in four media within 15 min. The dissolution rate of the amoxicillin medicine prepared in the comparative example is obviously inferior to that of the examples.
(3) Examples 1-11 and comparative examples 1-3 were tested for stability, respectively.
To further verify the stability of the amoxicillin drugs provided by the present invention, the amoxicillin drugs prepared in examples 1-11 and comparative examples 1-3 were subjected to accelerated testing and compared with commercially available formulations. The test conditions were 40 ℃ for 6 months.
Table 3: stability results (%)
Figure BDA0003088810130000112
Figure BDA0003088810130000121
Figure BDA0003088810130000131
As shown in the results of table 3, the amoxicillin drugs prepared in the examples showed good stability and dissolution, with stable impurity levels and lower than the commercial reference formulation.
In conclusion, the amoxicillin medicine prepared by the embodiment of the invention has high yield, can realize rapid dissolution in various media, and has stable impurity level and strong stability in the lofting process.

Claims (10)

1. The amoxicillin drug is characterized by comprising the following components: amoxicillin, filler and binder; the adhesive is crospovidone.
2. The amoxicillin drug of claim 1, wherein the binder is present in an amount of 2-5% by weight of the amoxicillin drug.
3. The amoxicillin drug of claim 1, wherein the particle size distribution of amoxicillin is D10: 2.5-10.0 μm, D50: 7.0-35.0 μm, D90: 12.0-55.0 μm; the particle size distribution of the filler is D10: 3.0-9.0 μm, D50: 20.0-70.0 μm, D90: 90.0-230.0 μm.
4. An amoxicillin drug according to claim 3, characterized in that the particle size distribution of said amoxicillin is D10: 2.5-7.0 μm, D50: 7.0-20.0 μm, D90: 12.0-40.0 μm; the particle size distribution of the filler is D10: 4.0-9.0 μm, D50: 30.0-70.0 μm, D90: 130.0-220.0 μm.
5. An amoxicillin drug according to claim 4, characterized in that the particle size distribution of the filler is D10: 5.0-8.0 μm, D50: 40.0-60.0 μm, D90: 150.0-200.0 μm.
6. An amoxicillin drug according to any of the claims 1-5, characterized by comprising the following components in mass percent: 10-20% of amoxicillin, 75-88% of filling agent and 2-5% of adhesive.
7. The amoxicillin drug according to claim 6, characterized by comprising the following components in mass percent: 10-15% of amoxicillin, 80-88% of filling agent and 2-5% of adhesive.
8. An amoxicillin pharmaceutical according to any of the claims 1-5, characterized in that the filler is selected from at least one of sucrose, starch, dextrin or microcrystalline cellulose.
9. A process for the preparation of an amoxycillin formulation as claimed in any one of claims 1 to 8, which comprises the steps of:
weighing amoxicillin, a filling agent and a binding agent, mixing, dry-pressing and granulating to obtain the amoxicillin medicine.
10. The method according to claim 9, wherein the pressure of the dry pressure is 60 to 90bar, and the sample feeding speed during the dry pressure is 50 to 80 rpm.
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