CN103142541A - Stable montelukast sodium capsule - Google Patents
Stable montelukast sodium capsule Download PDFInfo
- Publication number
- CN103142541A CN103142541A CN 201210323589 CN201210323589A CN103142541A CN 103142541 A CN103142541 A CN 103142541A CN 201210323589 CN201210323589 CN 201210323589 CN 201210323589 A CN201210323589 A CN 201210323589A CN 103142541 A CN103142541 A CN 103142541A
- Authority
- CN
- China
- Prior art keywords
- menglusitena
- silicon dioxide
- capsule
- capsule according
- accounts
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of medicine, and in particular to a stable montelukast sodium capsule. The capsule is characterized by containing montelukast sodium with a therapeutically effective amount, a certain amount of silica and other pharmaceutically acceptable excipients. The above components are directly filled into capsules to prepare the montelukast sodium preparation capable of preventing moisture adsorption and light decomposition of effective components; and the process is simple, controllable, has good storage stability, and saves cost.
Description
Technical field
The present invention relates to a kind of stable montelukast preparation of sodium, relate to particularly the Menglusitena capsule, belong to medical technical field.
Background technology
Menglusitena (Montelukast Sodium), chemistry is by name: (+)-1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolyl)-vinyl] phenyl]-3-[2-(1-hydroxyl-1-Methylethyl) phenyl] propyl group] sulfur] methyl] cyclopropaneacetic acid list sodium salt, be white or off-white color crystalline powder, odorless, have draw moist, be soluble in methanol, ethanol, acetone, DMF, its structural formula is as follows:
Montelukast is a kind of high specific cysteinyl leukotriene receptor antagonist, the interaction between its blocking-up cysteinyl leukotriene and receptor, thus the blocking-up trachea reaches the purpose of Control of asthma to the reaction of leukotriene.Studies show that montelukast has affinity and the selectivity of height to the CysLT1 receptor.Montelukast can effectively suppress LTC4, LTD4 and LTE4 and LTC4 that the CysLT1 receptors bind produces, LTD4 and LTE4 the physiological effect effect and without any receptor agonist activity.Along with more deep to the understanding of leukotriene and receptor antagonist thereof, new one studies show that, montelukast can improve pulmonary function and the airway reactivity of 2-5 year asthmatic children, thereby improves symptoms of asthma, Control of asthma outbreak and increasing the weight of.It is found that simultaneously montelukast not only can improve the pulmonary function of asthmatic patient, and in all many-sides such as antiinflammatory, immunity, important using value is arranged also.Menglusitena is the sodium salt of montelukast, and BCS is categorized as the I class, and due to its unique chemical constitution, its oral administration biaavailability, clinical efficacy and safety all are better than similar drugs in the past.
Menglusitena is by Merck ﹠ Co., Inc.'s Development and Production, is best-selling treating asthma medicine in the world at present.Since 1998, successively in the listing of a plurality of countries and regions, existing dosage form has Film coated tablets, granule, chewable tablet, oral cavity disintegration tablet.Menglusitena has hygroscopicity, and sees light meeting variable color, decomposition, and above-mentioned dosage form adopts wet granulation mostly, preparation time is long, easily cause related substance to raise, and drying time is long, the bad control of temperature, drying course easily make the soluble component migration, cause content to descend.
Patent of invention CN101773481A discloses a kind of chewable tablet that contains Menglusitena, by Menglusitena, microcrystalline Cellulose, mannitol, 4%PVPK30 alcoholic solution, zinc stearate and opacifier, although add opacifier can reduce to a certain extent light to the effect of Menglusitena in prescription, but increasing, adjuvant may cause the related substance increase, and adopt wet granulation to increase this step of particle drying, make production efficiency low, granule drying under hygrothermal environment also may make content reduce and related substance raises.Patent of invention CN101732268A discloses a kind of preparation method of montelukast sodium tablet, adopt dry granulation, direct compression, some impacts of having avoided wet granulation to cause, but dry granulation more complicated, higher to equipment requirements, and the tablet stability that makes do not improve yet, and meets the same decomposition easy to change of light.Patent of invention CN1961867A discloses a kind of montelukast sodium granules, patent of invention CN1628666A discloses a kind of montelukast sodium dispersible tablets, the preparation method of foregoing invention patent is all to adopt traditional handicraft to make, easily introduce related substance in preparation and dry run, the preparation stability that makes is poor, sees light decomposition easy to change.
The present invention launches for the stability that overcomes above-mentioned montelukast preparation of sodium and complicated process of preparation problem just.
Summary of the invention
The present invention adds silicon dioxide to improve its mobility in montelukast sodium compositions, then with its direct fill capsule, preparation technology is simple, need just can not make powder flowbility reach the requirement of fill capsule through this step of wet granulation.The capsule 's content loading amount that is prepared into is qualified, can avoid light on the impact of raw material, better stability of preparation.In addition, we find to add in prescription silicon dioxide can effectively improve the hygroscopicity of crude drug in experiment, and related substance is reduced, and also find to add a certain amount of silicon dioxide can accelerate the disintegrate of capsule, improve the dissolution rate of montelukast natrium capsule.
More specifically, the present invention comprises following technical scheme:
(1) a kind of Menglusitena capsule, comprise active component Menglusitena, silicon dioxide and pharmaceutically acceptable adjuvant, it is characterized in that Menglusitena Capsule content preparation process first and in prescription is mixed with Menglusitena after the first mixing of part silicon dioxide with other adjuvant again.
(2) Menglusitena capsule described according to (1) is characterized in that silicon dioxide accounts for the 1%-5% of weight of formulation.
(3) Menglusitena capsule described according to (1) is characterized in that silicon dioxide accounts for the 3%-5% of weight of formulation, and that a part of silicon dioxide that wherein first mixes with raw material accounts for the 60%-80% of silicon dioxide total amount in prescription.
(4) Menglusitena capsule described according to (1) is characterized in that silicon dioxide accounts for the 3%-5% of weight of formulation, and that a part of silicon dioxide that wherein first mixes with raw material accounts for the 60%-70% of silicon dioxide total amount in prescription.
(5) Menglusitena capsule described according to (1) is characterized in that Menglusitena accounts for the 1%-10% of weight of formulation.
(6) Menglusitena capsule described according to (1) is characterized in that Menglusitena accounts for the 2%-8% of weight of formulation.
(7) Menglusitena capsule described according to (1) is characterized in that Menglusitena accounts for the 4%-6% of weight of formulation.
(8) Menglusitena capsule described according to (1) is characterized in that described pharmaceutically acceptable adjuvant is selected from one or more in filler, disintegrating agent, lubricant.
(9) Menglusitena capsule described according to (1) is characterized in that described filler is selected from lactose, mannitol, sorbitol etc., preferred lactose.
(10) Menglusitena capsule described according to (1), it is characterized in that described disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl methylcellulose, preferred polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose.
(11) Menglusitena capsule described according to (1) is characterized in that described lubricant is selected from magnesium stearate.
(12) Menglusitena capsule described according to (1), is characterized in that containing in capsule shells lucifuge composition such as titanium dioxide, yellow ferric oxide etc.
, the specific embodiment
The specific embodiment of form, be described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following examples.
Embodiment 1 Menglusitena capsule
| The label composition | Part by weight (%) |
| Menglusitena | 5 |
| Microcrystalline Cellulose | 38.5 |
| Cross-linking sodium carboxymethyl cellulose | 6 |
| Lactose | 46.5 |
| Colloidal silica | 3 |
| Magnesium stearate | 1 |
Preparation technology: part silicon dioxide (2%) in Menglusitena and prescription is crossed after 30 mesh sieve mixings with lactose, the microcrystalline Cellulose of recipe quantity crossed the 30 mesh sieve equivalent mixing that progressively increases, the cross-linking sodium carboxymethyl cellulose, residue silicon dioxide, the magnesium stearate that add recipe quantity, mixing, the fill capsule.
Embodiment 2 Menglusitena capsules
| The label composition | Part by weight (%) |
| Menglusitena | 4 |
| Microcrystalline Cellulose | 36 |
| Cross-linking sodium carboxymethyl cellulose | 5 |
| Lactose | 50 |
| Colloidal silica | 4 |
| Magnesium stearate | 1 |
Preparation technology: part silicon dioxide (2.5%) in Menglusitena and prescription is crossed after 30 mesh sieve mixings with lactose, the microcrystalline Cellulose of recipe quantity crossed the 30 mesh sieve equivalent mixing that progressively increases, the cross-linking sodium carboxymethyl cellulose, residue silicon dioxide, the magnesium stearate that add recipe quantity, mixing, the fill capsule.
Embodiment 3:
The Menglusitena capsule
| The label composition | Part by weight (%) |
| Menglusitena | 6 |
| Microcrystalline Cellulose | 42 |
| Polyvinylpolypyrrolidone | 6 |
| Lactose | 40 |
| Colloidal silica | 5 |
| Magnesium stearate | 1 |
Preparation technology: part silicon dioxide (3%) in Menglusitena and prescription is crossed after 30 mesh sieve mixings with lactose, the microcrystalline Cellulose of recipe quantity crossed the 30 mesh sieve equivalent mixing that progressively increases, the cross-linking sodium carboxymethyl cellulose, residue silicon dioxide, the magnesium stearate that add recipe quantity, mixing, the fill capsule.
Comparative example's 1 Menglusitena capsule
| The label composition | Part by weight (%) |
| Menglusitena | 5 |
| Microcrystalline Cellulose | 38.5 |
| Cross-linking sodium carboxymethyl cellulose | 5 |
| Lactose | 47.5 |
| Colloidal silica | 1 |
| Magnesium stearate | 1 |
Preparation technology: with Menglusitena with cross the 30 mesh sieve equivalent mixing that progressively increases with lactose, the microcrystalline Cellulose of recipe quantity, add cross-linking sodium carboxymethyl cellulose, silicon dioxide, the magnesium stearate of recipe quantity, mixing, fill capsule.
Comparative example's 2 Menglusitena sheets
| The label composition | Part by weight (%) |
| Menglusitena | 5 |
| Microcrystalline Cellulose | 36.5 |
| Cross-linking sodium carboxymethyl cellulose (in add) | 4 |
| Cross-linking sodium carboxymethyl cellulose (adding) | 4 |
| Lactose | 46.1 |
| Hyprolose | 0.4 |
| Colloidal silica | 1 |
| Magnesium stearate | 1 |
Preparation technology: with Menglusitena with cross the 30 mesh sieve equivalent mixing that progressively increases with lactose, the microcrystalline Cellulose of recipe quantity, add recipe quantity in add after cross-linking sodium carboxymethyl cellulose hyprolose solution soft material processed with 2%, 18 mesh sieves are granulated, granule is dry under 50 ℃ of conditions, controls granule moisture content in 3.0%, 24 order granulate, with add cross-linking sodium carboxymethyl cellulose, silica sol and magnesium stearate mix homogeneously, measure montelukast sodium content in granule, determine that sheet is heavy, tabletting and get final product.
Comparative example's 3 Menglusitena Film coated tablets
| The label composition | Part by weight (%) |
| Menglusitena | 4 |
| Microcrystalline Cellulose | 36.5 |
| Cross-linking sodium carboxymethyl cellulose (in add) | 4 |
| Cross-linking sodium carboxymethyl cellulose (adding) | 4 |
| Lactose | 50.5 |
| Hyprolose | 0.5 |
| Magnesium stearate | 1 |
Preparation technology: with Menglusitena with cross the 30 mesh sieve equivalent mixing that progressively increases with lactose, the microcrystalline Cellulose of recipe quantity, add recipe quantity in add after cross-linking sodium carboxymethyl cellulose hyprolose solution soft material processed with 2%, 18 mesh sieves are granulated, and granule is dry under 50 ℃ of conditions, control granule moisture content in 3.0%, 24 order granulate, with add cross-linking sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, measure montelukast sodium content in granule, determine that sheet is heavy, tabletting, film coating and get final product.
Comparative example's 4 montelukast sodium granules
| The label composition | Part by weight (%) |
| Menglusitena | 5 |
| Microcrystalline Cellulose | 38.5 |
| Cross-linking sodium carboxymethyl cellulose (in add) | 6 |
| Lactose | 49.5 |
| Hyprolose | 1 |
Preparation technology: with Menglusitena with cross the 30 mesh sieve equivalent mixing that progressively increases with lactose, the microcrystalline Cellulose of recipe quantity, add recipe quantity in add after cross-linking sodium carboxymethyl cellulose hyprolose solution soft material processed with 2%, 14 mesh sieves are granulated, granule is dry under 50 ℃ of conditions, control granule moisture content in 3.0%, 16 mesh sieve granulate are measured montelukast sodium content in granule, determine every bag of Packing Unit.
Relatively the embodiment of the present invention 1 and the prepared oxiracetam preparation of comparative example 1 are placed related substance growth pattern after 10 days according to influence factor's test method (two appendix of Chinese Pharmacopoeia version in 2010), be respectively to place 10 days under 4500lx ± 500lx condition in 60 ℃ ± 2 ℃ of high temperature, high humidity RH92.5% and illumination respectively, investigate the related substance growth pattern.The results are shown in Table 1, table 2, table 3:
Table 1 embodiment and the comparative example related substance growth pattern under 60 ℃ ± 2 ℃ of high temperature:
Table 2 embodiment and the comparative example related substance growth pattern under high humidity RH92.5%:
Table 3 embodiment and the comparative example related substance growth pattern under illumination 4500lx ± 500lx:
By influence factor's result of the test as can be known, after placing 10 days under 60 ℃ of high temperature, high humidity RH92.5%, illumination 4500lx ± 500lx condition, adopting Menglusitena capsule and the comparative example 3(Menglusitena Film coated tablets of the present invention's preparation) related substance all increasess slowly, but because the present invention need not pass through this step of wet granulation, preparation technology of the present invention is simpler, 0 day related substance of preparation of preparation is lower, has improved the safety of montelukast preparation of sodium and has provided cost savings.Separately known by comparative example 1 to add a certain amount of silicon dioxide to play certain desiccation to preparation in prescription, reduce the growth of related substance.
Claims (10)
1. Menglusitena capsule, comprise active component Menglusitena, silicon dioxide and pharmaceutically acceptable adjuvant, it is characterized in that Menglusitena Capsule content preparation process first and in prescription is mixed with Menglusitena after the first mixing of part silicon dioxide with other adjuvant again.
2. Menglusitena capsule according to claim 1, is characterized in that silicon dioxide accounts for the 1%-5% of weight of formulation.
3. Menglusitena capsule according to claim 1, is characterized in that silicon dioxide accounts for the 3%-5% of weight of formulation, and that a part of silicon dioxide that wherein first mixes with raw material accounts for the 60%-80% of silicon dioxide total amount in prescription.
4. Menglusitena capsule according to claim 3, is characterized in that silicon dioxide accounts for the 3%-5% of weight of formulation, and that a part of silicon dioxide that wherein first mixes with raw material accounts for the 60%-70% of silicon dioxide total amount in prescription.
5. Menglusitena capsule according to claim 1, is characterized in that Menglusitena accounts for the 2%-8% of weight of formulation.
6. Menglusitena capsule according to claim 1, is characterized in that Menglusitena accounts for the 4%-6% of weight of formulation.
7. Menglusitena capsule according to claim 1, is characterized in that described pharmaceutically acceptable adjuvant is selected from one or more in filler, disintegrating agent, lubricant.
8. Menglusitena capsule according to claim 1, is characterized in that described filler is selected from lactose, mannitol, sorbitol etc., preferred lactose.
9. Menglusitena capsule according to claim 1, it is characterized in that described disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl methylcellulose, preferred polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose; Described lubricant is selected from magnesium stearate.
10. Menglusitena capsule according to claim 1, is characterized in that containing in capsule shells lucifuge composition such as titanium dioxide, yellow ferric oxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210323589 CN103142541A (en) | 2012-09-05 | 2012-09-05 | Stable montelukast sodium capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210323589 CN103142541A (en) | 2012-09-05 | 2012-09-05 | Stable montelukast sodium capsule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103142541A true CN103142541A (en) | 2013-06-12 |
Family
ID=48541057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210323589 Pending CN103142541A (en) | 2012-09-05 | 2012-09-05 | Stable montelukast sodium capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103142541A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103417509A (en) * | 2013-08-15 | 2013-12-04 | 华北制药河北华民药业有限责任公司 | Cefprozil tablet and preparation method thereof |
| CN104644605A (en) * | 2013-11-25 | 2015-05-27 | 天津汉瑞药业有限公司 | Stable capsule preparation containing montelukast and preparation method of capsule preparation |
| CN105769872A (en) * | 2014-12-25 | 2016-07-20 | 成都康弘药业集团股份有限公司 | Rapidly-dissolving mosapride citrate composition |
| CN108014089A (en) * | 2017-12-13 | 2018-05-11 | 合肥凯石医药科技有限公司 | A kind of Montelukast Sodium enteric-coated pellet capsule of stabilization and preparation method thereof |
-
2012
- 2012-09-05 CN CN 201210323589 patent/CN103142541A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103417509A (en) * | 2013-08-15 | 2013-12-04 | 华北制药河北华民药业有限责任公司 | Cefprozil tablet and preparation method thereof |
| CN103417509B (en) * | 2013-08-15 | 2015-04-29 | 华北制药河北华民药业有限责任公司 | Cefprozil tablet and preparation method thereof |
| CN104644605A (en) * | 2013-11-25 | 2015-05-27 | 天津汉瑞药业有限公司 | Stable capsule preparation containing montelukast and preparation method of capsule preparation |
| CN105769872A (en) * | 2014-12-25 | 2016-07-20 | 成都康弘药业集团股份有限公司 | Rapidly-dissolving mosapride citrate composition |
| CN105769872B (en) * | 2014-12-25 | 2019-05-03 | 成都康弘药业集团股份有限公司 | A kind of mosapride citrate composition of Fast Stripping |
| CN108014089A (en) * | 2017-12-13 | 2018-05-11 | 合肥凯石医药科技有限公司 | A kind of Montelukast Sodium enteric-coated pellet capsule of stabilization and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210228722A1 (en) | Quinoline derivative-containing pharmaceutical composition | |
| KR102006000B1 (en) | Capsule formulation comprising montelukast or a pharmaceutically acceptable salt thereof, and levocetirizine or a pharmaceutically acceptable salt thereof | |
| DK2356989T3 (en) | Stable tablet containing 4,5-epoxymorphinane derivative | |
| CN105287411A (en) | Perampanel dispersible tablet and preparation method thereof | |
| CN103284962B (en) | Moxifloxacin dispersible tablet and preparation method | |
| CN105919962A (en) | Dabigatran tablet, and preparation method and application thereof | |
| CN103142541A (en) | Stable montelukast sodium capsule | |
| EA030433B1 (en) | Enteric tablet | |
| CN106999483A (en) | A kind of pharmaceutical composition containing quinoline or its salt | |
| EP2934488B1 (en) | A pharmaceutical composition containing candesartan cilexetil and amlodipine | |
| CN103520169B (en) | Mirtazapine tablet and preparation method thereof | |
| CN102068415B (en) | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof | |
| CN105816436B (en) | A kind of Pantoprazole enteric-coated micro-pill, Pantoprazole enteric slow-release tablet agent and preparation method thereof | |
| CN104644632A (en) | Orally taken tablet containing Azilsartan and benzenesulfonate amlodipine and preparation method thereof | |
| CN105636581A (en) | Pharmaceutical composition | |
| CN105435237B (en) | A kind of prasugrel hydrochloride pharmaceutical composition, tablet and preparation method thereof | |
| WO2013077829A1 (en) | Water-soluble pharmaceutical granules | |
| CN104000821B (en) | Oral double-layer tablet containing telmisartan and amlodipine besylate and preparation method thereof | |
| CN112704740B (en) | Montelukast resin compound and preparation method and application thereof | |
| CN109498578A (en) | Stable Olanzapine composition and preparation method thereof | |
| CN103768029B (en) | High stability lafutidine tablets and preparation process thereof | |
| CN109939237A (en) | Preparation method containing Montelukast Sodium oral disintegrating tablet | |
| KR101249783B1 (en) | Pharmaceutical composition and method of fabricating the same | |
| CN106619618A (en) | Valsartan medicinal composition and preparation method thereof | |
| JP3935539B2 (en) | Pharmaceutical composition containing ketotifen fumarate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130612 |