CN112641738A - Azithromycin tablet composition - Google Patents
Azithromycin tablet composition Download PDFInfo
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- CN112641738A CN112641738A CN202011525598.8A CN202011525598A CN112641738A CN 112641738 A CN112641738 A CN 112641738A CN 202011525598 A CN202011525598 A CN 202011525598A CN 112641738 A CN112641738 A CN 112641738A
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- Prior art keywords
- azithromycin
- polyvinyl alcohol
- meglumine
- lactose
- composition
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- 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
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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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- Life Sciences & Earth 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)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Otolaryngology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an azithromycin composition and a preparation method thereof, belonging to the technical field of pharmacy. The technical scheme of the invention is as follows: an azithromycin tablet composition, in unit dose, comprising: 100-250mg of azithromycin, 20-80mg of microcrystalline cellulose, 20-50mg of lactose, 5-50mg of polyvinyl alcohol, 1-10mg of meglumine and 2mg of magnesium stearate. The invention provides a stable azithromycin tablet composition.
Description
Technical Field
The invention relates to an azithromycin composition and a preparation method thereof, belonging to the technical field of pharmacy.
Background
The azithromycin is suitable for treating acute pharyngitis and acute tonsillitis caused by streptococcus pyogenes; sinusitis, otitis media, acute bronchitis and acute attack of chronic bronchitis caused by sensitive bacteria; pneumonia caused by streptococcus pneumoniae, haemophilus influenzae, and mycoplasma pneumoniae, etc.
According to the chemical structure of the azithromycin, the azithromycin is a macrolide drug and has poor stability. Stability experiments show that in the storage process, azithromycin tablets have a degradation phenomenon, and impurities A, B and total impurities of the azithromycin tablets are increased to a great extent, so that the medication safety is influenced. In the prior art, anhydrous calcium hydrogen phosphate is used as a filler to solve the problem of impurity growth, the surface of the anhydrous calcium phosphate which is not crushed is acidic, and the surface of the anhydrous calcium hydrogen phosphate which is crushed is alkaline (R.C. Roo, handbook of pharmaceutical excipients (fourth edition) (M). Beijing: chemical industry Press, 2005: 89). In the original research, in order to avoid the existence of water, a direct compression process is adopted in the preparation process, and the non-crushed anhydrous calcium hydrophosphate is selected as a filler, and the anhydrous calcium hydrophosphate is crushed under pressure in the tabletting process, so that the anhydrous calcium hydrophosphate is changed into alkaline. The invention adopts two auxiliary materials of polyvinyl alcohol and meglumine to dissolve, and an alkaline film is formed on the surface of the medicine through a granulation process, and the effect of inhibiting the degradation of the azithromycin bulk drug is achieved by inhibiting the dissolution of the azithromycin bulk drug.
Disclosure of Invention
The purpose of the invention is as follows: solves the stability problem of the azithromycin tablets, and provides safe and effective medicaments for clinic.
The applicant tests and finds that the addition of polyvinyl alcohol and meglumine into the prescription of the azithromycin tablet can inhibit the degradation of the azithromycin tablet and avoid the problem of impurity rise.
The technical scheme of the invention is as follows:
an azithromycin tablet composition contains pharmaceutical adjuvants of polyvinyl alcohol and meglumine.
The polyvinyl alcohol is easy to dissolve in water and can form a film on the surface of the material. The meglumine is an alkaline material, and because the azithromycin is easy to dissolve in an acidic medium and insoluble in an alkaline environment, the alkaline environment of the azithromycin bulk drug can be maintained after the meglumine is added, so that the dissolution is reduced, and the stability of the azithromycin is improved. Polyvinyl alcohol and meglumine are used as adhesive and adhered to the surface of azithromycin to form an alkaline film, so as to achieve the protection effect. Because the protective film has water solubility, the dissolution stability of the product during the stability period can be ensured.
The technical scheme of the invention is as follows:
an azithromycin tablet composition, in unit dose, comprising: 100-250mg of azithromycin, 20-80mg of microcrystalline cellulose, 20-50mg of lactose, 5-50mg of polyvinyl alcohol, 1-10mg of meglumine and 2mg of magnesium stearate.
Preferably, the mass ratio of the polyvinyl alcohol to the meglumine of the azithromycin composition is 5-20: 1.
Preferably, the azithromycin composition of the invention comprises: 100-250mg of azithromycin, 30-60mg of microcrystalline cellulose, 30-40mg of lactose and 10-40mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 5-20: 1.
Preferably, the azithromycin composition of the invention comprises: 100mg of azithromycin, 40mg of microcrystalline cellulose, 40mg of lactose and 40mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 20: 1.
Preferably, the azithromycin composition of the invention comprises: 250mg of azithromycin, 60mg of microcrystalline cellulose, 40mg of lactose and 30mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 6: 1.
Preferably, the azithromycin composition of the invention comprises: 100mg of azithromycin, 50mg of microcrystalline cellulose, 50mg of lactose and 50mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 5: 1.
The preparation method of the azithromycin tablet comprises the following steps:
firstly, dissolving polyvinyl alcohol and meglumine in water, and uniformly mixing;
secondly, placing azithromycin, microcrystalline cellulose and lactose in a fluidized bed according to the prescription amount, spraying aqueous solution of polyvinyl alcohol and meglumine, granulating and finishing granules;
and thirdly, adding magnesium stearate into the material obtained in the second step, uniformly mixing, and tabletting.
Has the advantages that: the invention provides a stable azithromycin tablet composition, wherein a solution of polyvinyl alcohol and meglumine is sprayed into a material as an adhesive, and the adhesive is dried and attached to the surface of particles to form an alkaline protective film. Because azithromycin is insoluble under alkaline conditions, the presence of molecular azithromycin is reduced, thereby inhibiting the degradation of azithromycin.
Examples and comparative examples
Example 1 azithromycin 100g, microcrystalline cellulose 30g, lactose 30g, polyvinyl alcohol 5g, meglumine 1g, magnesium stearate 2 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section.
Example 2 azithromycin 100g, microcrystalline cellulose 50g, lactose 20g, polyvinyl alcohol 50g, meglumine 10g, magnesium stearate 2 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section.
Example 3 azithromycin 100g, microcrystalline cellulose 20g, lactose 50g, polyvinyl alcohol 10g, meglumine 5g, magnesium stearate 2 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section.
Example 4 azithromycin 250g, microcrystalline cellulose 50g, lactose 30g, polyvinyl alcohol 40g, meglumine 2g, magnesium stearate 2 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section.
Example 5 azithromycin 250g, microcrystalline cellulose 60g, lactose 40g, polyvinyl alcohol 30g, meglumine 5g, magnesium stearate 2 g. 1000 tablets were prepared according to the preparation method described in the technical scheme section.
Comparative example 1 (see example 1)
100g of azithromycin, 30g of microcrystalline cellulose, 30g of lactose, 1g of polyvinyl alcohol, 5g of meglumine and 2g of magnesium stearate. 1000 tablets were prepared according to the following preparation method.
The first step is as follows: dissolving polyvinyl alcohol and meglumine in water, and mixing uniformly.
The second step is that: azithromycin, microcrystalline cellulose and lactose in the prescribed dose are put into a fluidized bed, sprayed with polyvinyl alcohol and aqueous solution of meglumine, and granulated. And (5) finishing.
The third step: and adding magnesium stearate into the materials obtained in the second step, uniformly mixing, and tabletting.
Comparative example 2 (see example 1)
100g of azithromycin, 30g of microcrystalline cellulose, 30g of lactose, 10g of polyvinyl alcohol and 2g of magnesium stearate.
1000 tablets were prepared according to the following preparation method.
The first step is as follows: dissolving polyvinyl alcohol in water, and mixing uniformly.
The second step is that: azithromycin, microcrystalline cellulose and lactose in a prescription dose are placed in a fluidized bed, and polyvinyl alcohol aqueous solution is sprayed into the fluidized bed for granulation. And (5) finishing.
The third step: and adding magnesium stearate into the materials obtained in the second step, uniformly mixing, and tabletting.
Test example 1: 100 tablets of the products of examples 1 to 5 and comparative example 1 were taken, respectively packaged in aluminum plastic, placed under the acceleration (40 ℃/75% RH) condition, and the dissolution rate of each sample was determined according to the azithromycin tablet dissolution rate method in the chinese pharmacopoeia 2020 edition. The results are shown in Table 1
TABLE 1 dissolution behavior under accelerated conditions
Table 1 the data illustrates: when the amount of polyvinyl alcohol used is small, the dissolution of the tablet is low. Under accelerated conditions, less polyvinyl alcohol does not provide sufficient hydrophilicity due to the coalescence of lactose, and dissolution is reduced.
Test example 2: 100 pieces of the products of examples 1 to 5 and comparative example 2 were each separately packaged in aluminum plastic and placed under accelerated conditions (40 ℃/75% RH) and the impurity levels were measured by high performance liquid chromatography for 0 day and 6 months of acceleration, the results of which are shown in Table 2.
TABLE 2 impurity conditions under accelerated conditions
Table 2 the data illustrates: in comparative example 2, no meglumine was present, and the impurities increased significantly under accelerated conditions compared to the examples. The meglumine can provide an alkaline environment for the azithromycin, and can keep the impurities of the product stable.
The above results illustrate that: according to the invention, through reasonable adjustment of the prescription and combination of the preparation method disclosed by the invention, a product with stable impurities under an accelerated condition is obtained.
Claims (7)
1. An azithromycin tablet composition is characterized in that the composition of unit dose contains 100-250mg of azithromycin, 20-80mg of microcrystalline cellulose, 20-50mg of lactose, 5-50mg of polyvinyl alcohol, 1-10mg of meglumine and 2mg of magnesium stearate.
2. The azithromycin composition of claim 1, wherein the mass ratio of polyvinyl alcohol to meglumine is in the range of 5-20: 1.
3. The azithromycin composition as claimed in claim 1, which comprises 100-250mg of azithromycin, 30-60mg of microcrystalline cellulose, 30-40mg of lactose and 10-40mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is in the range of 5-20: 1.
4. The azithromycin composition of claim 1, which comprises 100mg of azithromycin, 40mg of microcrystalline cellulose, 40mg of lactose and 40mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 20: 1.
5. The azithromycin composition of claim 1, which comprises 250mg of azithromycin, 60mg of microcrystalline cellulose, 40mg of lactose and 30mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 6: 1.
6. The azithromycin composition according to claim 1, which comprises 100mg of azithromycin, 50mg of microcrystalline cellulose, 50mg of lactose and 50mg of polyvinyl alcohol, wherein the mass ratio of the polyvinyl alcohol to the meglumine is 5: 1.
7. A process for preparing the azithromycin composition of claim 1, comprising the steps of:
firstly, dissolving polyvinyl alcohol and meglumine in water, and uniformly mixing;
secondly, placing azithromycin, microcrystalline cellulose and lactose in a fluidized bed according to the prescription amount, spraying aqueous solution of polyvinyl alcohol and meglumine, granulating and finishing granules;
and thirdly, adding magnesium stearate into the material obtained in the second step, uniformly mixing, and tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011525598.8A CN112641738A (en) | 2020-12-22 | 2020-12-22 | Azithromycin tablet composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011525598.8A CN112641738A (en) | 2020-12-22 | 2020-12-22 | Azithromycin tablet composition |
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| Publication Number | Publication Date |
|---|---|
| CN112641738A true CN112641738A (en) | 2021-04-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011525598.8A Pending CN112641738A (en) | 2020-12-22 | 2020-12-22 | Azithromycin tablet composition |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022220669A1 (en) * | 2021-04-16 | 2022-10-20 | Garcia Perez Miguel Angel | Oral solid combination for the treatment of virus infection |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005030257A2 (en) * | 2003-09-30 | 2005-04-07 | Solubest Ltd. | Water soluble nanoparticles inclusion complexes |
| CN101491535A (en) * | 2008-01-26 | 2009-07-29 | 海南高升医药科技开发有限公司 | Method for preparing azithromycin composition with reduced bitter |
| CN107281155A (en) * | 2017-06-06 | 2017-10-24 | 扬子江药业集团四川海蓉药业有限公司 | A kind of azithromycin tablet and preparation method thereof |
-
2020
- 2020-12-22 CN CN202011525598.8A patent/CN112641738A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005030257A2 (en) * | 2003-09-30 | 2005-04-07 | Solubest Ltd. | Water soluble nanoparticles inclusion complexes |
| CN101491535A (en) * | 2008-01-26 | 2009-07-29 | 海南高升医药科技开发有限公司 | Method for preparing azithromycin composition with reduced bitter |
| CN107281155A (en) * | 2017-06-06 | 2017-10-24 | 扬子江药业集团四川海蓉药业有限公司 | A kind of azithromycin tablet and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| L. MIGUEL ET AL.: "LC determination of impurities in azithromycin tablets", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
| 国家药典委员会: "《中华人民共和国药典：20200年.四部》", 31 May 2020, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022220669A1 (en) * | 2021-04-16 | 2022-10-20 | Garcia Perez Miguel Angel | Oral solid combination for the treatment of virus infection |
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| PB01 | Publication | ||
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| TA01 | Transfer of patent application right |
Effective date of registration: 20210901 Address after: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Applicant after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Applicant before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Applicant before: Dijia Pharmaceutical Group Co.,Ltd. |
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| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210413 |