CN111437260A - Method for preparing memantine hydrochloride solid pharmaceutical composition - Google Patents
Method for preparing memantine hydrochloride solid pharmaceutical composition Download PDFInfo
- Publication number
- CN111437260A CN111437260A CN201910043317.6A CN201910043317A CN111437260A CN 111437260 A CN111437260 A CN 111437260A CN 201910043317 A CN201910043317 A CN 201910043317A CN 111437260 A CN111437260 A CN 111437260A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- active substance
- memantine hydrochloride
- solvent
- solid pharmaceutical
- 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.)
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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
- A61K31/13—Amines
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Abstract
The invention belongs to the field of medicines, relates to a method for preparing a memantine hydrochloride solid pharmaceutical composition capable of being orally administrated, solves the problem of low content of memantine hydrochloride caused by electrostatic adsorption loss in the preparation process of memantine hydrochloride solid pharmaceutical, and achieves unexpected technical effects.
Description
Technical Field
The invention belongs to the field of medicinal preparations, and particularly relates to a method for preparing a memantine hydrochloride solid medicinal composition, which solves the problem of content loss caused by electrostatic adsorption of a raw material medicament in a preparation process.
Background
Memantine hydrochloride is a novel medicine for treating Alzheimer Disease (AD), mainly acts on glutamine system in brain, acts by delaying release of excitatory neurotransmitter glutamate, and is the only N-methyl-D-aspartate receptor (NMDA) antagonist developed for Alzheimer disease. Memantine is currently approved in europe for the treatment of moderate to severe AD, and in the united states for the treatment of moderate to severe AD.
In our pharmaceutical research stage, the content of the prepared sample is found to be lower than 95%, and the phenomenon appears in a plurality of batches. A large amount of experimental data researches show that the memantine hydrochloride is static, so that the memantine hydrochloride is easy to be adsorbed due to the static effect in the sample preparation process to cause loss. After examining patents and documents, the raw materials often have electrostatic phenomena, and the solution is not obvious. In the research process, I screened a plurality of static electricity removing methods, and the approach related to the invention is the most effective and the simplest.
Disclosure of Invention
The memantine hydrochloride BCS is classified as I type, most of solid compositions are quickly dissolved, and most of the adopted processes are used for preparing the solid compositions after common wet granulation. Because memantine hydrochloride is easy to dissolve in water, the raw materials are added into the prescription in a preparation way or the raw materials and the auxiliary materials are fully mixed to avoid static electricity.
A process for the preparation of an orally administrable solid pharmaceutical composition of memantine hydrochloride by first preparing granules containing the active substance by wet granulation, wherein the active substance is treated with a solvent or a pharmaceutically acceptable excipient, and then converting the granules into a pharmaceutical composition by adding suitable additives.
The active substance is dissolved in a solvent and this solution is added during wet granulation to produce granules of the active substance. The solvent is purified water or ethanol water solution. The concentration of the ethanol water solution is 10% -60%.
When the temperature is lower, the active substance is not easy to dissolve in purified water or ethanol water solution, and can be rapidly dissolved by heating in water bath.
Mixing the active substance with excipient (starch or pregelatinized starch or mannitol), and repeatedly sieving or pulverizing.
The pharmaceutical composition is an orally disintegrating tablet, and the additive for meeting the requirement of disintegration is microcrystalline cellulose, so that the disintegration time limit can be greatly reduced.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following examples further describe the beneficial effects of the present invention, and the examples are for illustrative purposes only and do not limit the scope of the present invention.
Example 1
The prescription composition is as follows:
memantine hydrochloride 5.00%
Mannitol 30.00%
20.00 percent of starch
Low-substituted hydroxypropyl cellulose 20.00%
Microcrystalline cellulose 20.00%
4.00 percent of flavoring agent
Magnesium stearate 1.00%
The preparation process comprises the following steps:
dissolving memantine hydrochloride in 30% ethanol under stirring, and accelerating dissolution at constant temperature in water bath. Mixing mannitol, starch and part of low-substituted hydroxypropyl cellulose uniformly, adding memantine hydrochloride solution, granulating, rinsing the cup wall with solvent to obtain granules containing active ingredient, drying, mixing the granules containing active ingredient, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, correctant and magnesium stearate uniformly, and tabletting.
Example 2
The prescription composition is as follows:
memantine hydrochloride 5.00%
Mannitol 20.00%
Starch 30.00%
Low-substituted hydroxypropyl cellulose 20.00%
Microcrystalline cellulose 20.00%
4.00 percent of flavoring agent
Magnesium stearate 1.00%
The preparation process comprises the following steps:
dissolving memantine hydrochloride in 50% ethanol under stirring, and accelerating dissolution at constant temperature in water bath. Mixing mannitol, starch and part of low-substituted hydroxypropyl cellulose uniformly, adding memantine hydrochloride solution, granulating, rinsing the cup wall with solvent to obtain granules containing active ingredient, drying, mixing the granules containing active ingredient, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, correctant and magnesium stearate uniformly, and tabletting.
Example 3
The prescription composition is as follows:
memantine hydrochloride 5.00%
Mannitol 20.00%
Starch 30.00%
Low-substituted hydroxypropyl cellulose 20.00%
Microcrystalline cellulose 20.00%
4.00 percent of flavoring agent
Magnesium stearate 1.00%
The preparation process comprises the following steps:
memantine hydrochloride and starch are co-pulverized or sieved and mixed for 6 times in a pulverizer. Mixing mannitol and part of low-substituted hydroxypropyl cellulose, adding purified water, granulating to obtain granule containing active ingredient, drying, mixing the granule containing active ingredient, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, correctant, and magnesium stearate, and tabletting.
Example 4
The prescription composition is as follows:
memantine hydrochloride 5.00%
Mannitol 40.00%
Starch 30.00%
Low-substituted hydroxypropyl cellulose 20.00%
4.00 percent of flavoring agent
Magnesium stearate 1.00%
The preparation process comprises the following steps:
memantine hydrochloride and starch are co-pulverized or sieved and mixed for 6 times in a pulverizer. Mixing mannitol and part of low-substituted hydroxypropyl cellulose, adding purified water, granulating to obtain granule containing active ingredient, drying, mixing the granule containing active ingredient, low-substituted hydroxypropyl cellulose, correctant, and magnesium stearate, and tabletting.
Example 5
The prescription composition is as follows:
memantine hydrochloride 5.00%
Mannitol 20.00%
Starch 30.00%
Low-substituted hydroxypropyl cellulose 20.00%
Microcrystalline cellulose 20.00%
4.00 percent of flavoring agent
Magnesium stearate 1.00%
The preparation process comprises the following steps:
mixing memantine hydrochloride, mannitol, starch, and part of low-substituted hydroxypropyl cellulose, adding purified water, granulating to obtain granule containing active ingredient, drying, mixing the granule containing active ingredient, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, correctant, and magnesium stearate, and tabletting.
Detecting the content of memantine hydrochloride according to the quality standard of the memantine hydrochloride tablets in USP41 edition pharmacopeia, detecting the disintegration time limit of the orally disintegrating tablets according to the disintegration time limit inspection method of four parts 0921 in 'Chinese pharmacopeia' 2015 edition, and obtaining the result:
| test item | Example 1 | Example 2 | Example 3 | Example 4 | Example 5 |
| Content (wt.) | 99.87% | 101.21% | 98.89% | 97.91% | 91.23% |
| Disintegration time limit | Within 30s | Within 30s | Within 40s | Over 60s | Within 40s |
And (4) conclusion: the content of the example 1-4 is 95% -105%, which meets the requirement, while the content of the example 5 is 91.23%, which is low, which indicates that the loss of memantine hydrochloride in the preparation process is serious, and the content is unqualified. The disintegration time was less than 60 seconds and was acceptable except for example 4, while example 4 resulted in an unacceptable disintegration time due to the absence of microcrystalline cellulose when mixed with the active ingredient-containing granules. From examples 1 to 5, it is clear that the present invention is effective in preventing the loss of memantine hydrochloride and in a technique in which the disintegration time is acceptable.
Claims (9)
1. Process for the preparation of an orally administrable solid pharmaceutical composition of memantine hydrochloride, characterized in that granules containing the active substance are first prepared by wet granulation, wherein the active substance is treated with a solvent or with pharmaceutically acceptable excipients, and then the granules are converted into a pharmaceutical composition by adding suitable additives.
2. A process for the preparation of a pharmaceutical composition according to claim 1, characterized in that the active substance is dissolved in a solvent and the solution is added during wet granulation to obtain granules of the active substance.
3. The method according to claim 1 or 2, wherein the solvent is purified water or an aqueous ethanol solution.
4. The method according to claim 3, wherein the solvent is preferably an aqueous ethanol solution having a concentration of 10% (w/w) to 60% (w/w).
5. A method according to claim 2, wherein the active substance is dissolved in purified water or an aqueous solution of ethanol by heating in a water bath to rapidly dissolve the active substance.
6. A method according to claim 1 of preparing a pharmaceutical composition, wherein the active substance is mixed with the excipient thoroughly, by repeated sieving or co-crushing.
7. The method of claim 1 or 6, wherein the excipient is one or more of starch, pregelatinized starch, and mannitol.
8. The method of claim 1, wherein the pharmaceutical composition is an orally disintegrating tablet.
9. The method of claim 8 wherein the additive is microcrystalline cellulose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910043317.6A CN111437260A (en) | 2019-01-17 | 2019-01-17 | Method for preparing memantine hydrochloride solid pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910043317.6A CN111437260A (en) | 2019-01-17 | 2019-01-17 | Method for preparing memantine hydrochloride solid pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111437260A true CN111437260A (en) | 2020-07-24 |
Family
ID=71626920
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910043317.6A Pending CN111437260A (en) | 2019-01-17 | 2019-01-17 | Method for preparing memantine hydrochloride solid pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111437260A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709229A (en) * | 2005-06-10 | 2005-12-21 | 北京阜康仁生物制药科技有限公司 | Memantine hydrochloride orally disintegrating tablet and its preparing method |
| CN101069685A (en) * | 2002-12-16 | 2007-11-14 | 橘生药品工业株式会社 | Solid drug for oral use |
| CN101204378A (en) * | 2006-12-19 | 2008-06-25 | 北京德众万全药物技术开发有限公司 | Memantine hydrochloride oral medicine compound and its preparation method |
| US20100215740A1 (en) * | 2007-10-10 | 2010-08-26 | Rubicon Research Private Limited | Taste-masked orally disintegrating tablets of memantine hydrochloride |
| CN102740836A (en) * | 2009-04-24 | 2012-10-17 | 伊休蒂卡有限公司 | Method for the production of commercial nanoparticle and microparticle powders |
| CN103565774A (en) * | 2012-08-10 | 2014-02-12 | 石药集团中奇制药技术（石家庄）有限公司 | Glipizide controlled release composition as well as preparation method thereof |
-
2019
- 2019-01-17 CN CN201910043317.6A patent/CN111437260A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101069685A (en) * | 2002-12-16 | 2007-11-14 | 橘生药品工业株式会社 | Solid drug for oral use |
| CN1709229A (en) * | 2005-06-10 | 2005-12-21 | 北京阜康仁生物制药科技有限公司 | Memantine hydrochloride orally disintegrating tablet and its preparing method |
| CN101204378A (en) * | 2006-12-19 | 2008-06-25 | 北京德众万全药物技术开发有限公司 | Memantine hydrochloride oral medicine compound and its preparation method |
| US20100215740A1 (en) * | 2007-10-10 | 2010-08-26 | Rubicon Research Private Limited | Taste-masked orally disintegrating tablets of memantine hydrochloride |
| CN102740836A (en) * | 2009-04-24 | 2012-10-17 | 伊休蒂卡有限公司 | Method for the production of commercial nanoparticle and microparticle powders |
| CN103565774A (en) * | 2012-08-10 | 2014-02-12 | 石药集团中奇制药技术（石家庄）有限公司 | Glipizide controlled release composition as well as preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 周建平: "《药剂学》", 31 March 2016, 中国医药科技出版社 * |
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Application publication date: 20200724 |