CN102342924A - Medicine composition containing agomelatine - Google Patents
Medicine composition containing agomelatine Download PDFInfo
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- CN102342924A CN102342924A CN2010102458209A CN201010245820A CN102342924A CN 102342924 A CN102342924 A CN 102342924A CN 2010102458209 A CN2010102458209 A CN 2010102458209A CN 201010245820 A CN201010245820 A CN 201010245820A CN 102342924 A CN102342924 A CN 102342924A
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- agomelatine
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- magnesium stearate
- lactose
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Abstract
The invention belongs to the technical field of medicine, and discloses a medicine composition containing agomelatine prepared form components of, by weight: 11% to 25% of agomelatine, 30% to 65% of lactose, 11% to 40% of starch, 8% to 15% of carboxymethylstarch sodium, 0.5 to 5% of stearic acid, 0.6% to 2% of magnesium stearate, and 0.5% to 5% of silicon dioxide. As a result of experiments, preparations prepared with the medicine composition provided by the invention provide a better dissolution rate.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of pharmaceutical composition that contains agomelatine.
Background technology
The N-of agomelatine or formula (I) [2-(7-methoxyl group-1-naphthyl) ethyl] acetamide:
And the addition salts of its hydrate, crystal form and pharmaceutically acceptable acid or alkali has the valuable pharmacological activity: agomelatine is melatonin receptors agonist (MT1 and MT2 receptor) and 5-HT2C antagonist; This makes it have central nervous system's activity, especially in the treatment of serious symptom depression, seasonal affective disorder, sleep disordered, cardiovascular disease, digestive system disease, the insomnia that is caused by the time difference and fatigue, appetite disorder and obesity, activity is arranged.
Among European patent specification EP0 447 285 and the EP1 564 202 agomelatine, its preparation and the purposes in treatment have been described.
CN1287780C disclose comprise agomelatine can be in mouth dispersive pharmaceutical composition, it mainly is that form with tablet exists, and adopts the method preparation of direct compression; The hardness of tablet is 20 newton; Disintegrate jitter time in the oral cavity was less than 3 minutes, and this Orally disintegrating compositions possibly improve agomelatine in the intravital bioavailability of people, but in the oral cavity just directly fast disintegrate might cause the bad mouthfeel rapid release of medicine; Reduce patient's compliance; And reach the quick disintegrate in oral cavity, the hardness of tablet is generally smaller, and transportation and packing are brought difficulty.
What CN1981752A disclosed the oral mucosa that is used for agomelatine or sublingual administration can be at the dispersive pharmaceutical composition of mouth; This pharmaceutical composition uses
and other adjuvants;
be a kind of by 15% corn starch and 85% lactose monohydrate spray-dried-cohesion and the novel complexes processed; This adjuvant needs import; Cost an arm and a leg and the difficult legal qualification of being correlated with that obtains, be not suitable for the preparation suitability for industrialized production.
CN101152143A discloses the Pharmaceutical composition that contains agomelatine; This method is through adding the non-ionic hydrophilic surfactant in the pharmaceutical composition of agomelatine; Improve the bioavailability of agomelatine in human body; This invention possibly be able to improve the bioavailability of agomelatine in the human body; May cause mucosa injury but surfactant prolonged application or high concentration are used, and the agomelatine tablet bioavailability of producing at present meets the requirements, in preparation, adding the non-ionic hydrophilic surfactant can increase production cost undoubtedly.
CN101732296A discloses a kind of Pharmaceutical composition that contains agomelatine; The preparation that this method uses lactose, starch and sodium carboxymethylstarch and magnesium stearate to form; It should be noted that agomelatine is an insoluble drug and mobile poor; Be difficult to the dissolution of assurance product in the actual preparation production, and the method that this method uses equivalent to progressively increase is granulated use in being not suitable for producing greatly.
Can successfully prepare a kind of common agomelatine oral solid formulation, can guarantee that its uniform content degree is good, be applicable to pharmaceutical factory practical large-scale production again, and mouthfeel be good, preparation, packing and cost of transportation be cheap.Become problem demanding prompt solution.
Summary of the invention
Magnesium stearate and stearic acid use as lubricant in the present invention.Magnesium stearate is the stickiness powder, and mobile poor, blocking medicine is stripping from solid dosage forms, when consumption is excessive, can make the disintegrate (or stripping) of tablet slow, so in prescription, use minimum as far as possible concentration.Stearic acid has good lubrication, but than magnesium stearate slightly a little less than, less relatively to the harmful effect of tablet molding and disintegrate and medicine stripping.
The inventor is through lot of test; Discovery uses stearic acid and magnesium stearate as lubricant in the agomelatine pharmaceutical composition simultaneously, and lubrication is superior to using separately magnesium stearate, can effectively prevent sticking; Significantly improve the outward appearance of tablet, and effectively improve the dissolution of preparation.
The present invention realizes through following technical scheme:
A kind of pharmaceutical composition that contains agomelatine is made up of following ingredients and percentage by weight: 11%～25% agomelatine, 30%～65% lactose, 11%～40% starch, 8%～15% carboxymethylstach sodium, 0.5%～5% stearic acid, 0.6%～2% magnesium stearate, 0.5%～5% silicon dioxide.
A kind of pharmaceutical composition that contains agomelatine of the present invention is made up of 16.67% agomelatine, 53.33% lactose, 15% starch, 10% carboxymethylstach sodium, 3% stearic acid, 1% magnesium stearate, 1% silicon dioxide.
A kind of concrete preparation technology who contains the pharmaceutical composition of agomelatine of the present invention is: agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight, mix homogeneously; It is an amount of to add wetting agent, and the system soft material is granulated drying; Granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight, stearic acid, silicon dioxide add in the granule, mix homogeneously in blender; Add the magnesium stearate mix homogeneously, tabletting, coating promptly gets.
Embodiment
The present invention does further to set forth through following examples, but does not limit the present invention in any way.
Embodiment 1
| Composition | Weight % |
| Agomelatine | 16.67 |
| Lactose | 53.33 |
| Starch | 15 |
| Carboxymethylstach sodium | 10 |
| Stearic acid | 3 |
| Magnesium stearate | 1 |
| Silicon dioxide | 1 |
| Amount to | 100 |
Agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight, mix homogeneously; It is an amount of to add wetting agent, and the system soft material is granulated drying; Granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight, stearic acid, silicon dioxide add in the granule, mix homogeneously in blender; Add the magnesium stearate mix homogeneously, tabletting, coating promptly gets.
Embodiment 2
| Composition | Weight % |
| Agomelatine | 16.67 |
| Lactose | 54.33 |
| Starch | 15 |
| Carboxymethylstach sodium | 10 |
| Stearic acid | 2 |
| Magnesium stearate | 1 |
| Silicon dioxide | 1 |
| Amount to | 100 |
Agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight, mix homogeneously; It is an amount of to add wetting agent, and the system soft material is granulated drying; Granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight, stearic acid, silicon dioxide add in the granule, mix homogeneously in blender; Add the magnesium stearate mix homogeneously, tabletting, coating promptly gets.
Embodiment 3
| Composition | Weight % |
| Agomelatine | 11.57 |
| Lactose | 55.83 |
| Starch | 13 |
| Carboxymethylstach sodium | 11 |
| Stearic acid | 5 |
| Magnesium stearate | 0.6 |
| Silicon dioxide | 3 |
| Amount to | 100 |
Agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight, mix homogeneously; It is an amount of to add wetting agent, and the system soft material is granulated drying; Granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight, stearic acid, silicon dioxide add in the granule, mix homogeneously in blender; Add the magnesium stearate mix homogeneously, tabletting, coating promptly gets.
Embodiment 4
| Composition | Weight % |
| Agomelatine | 25 |
| Lactose | 42 |
| Starch | 14 |
| Carboxymethylstach sodium | 8 |
| Stearic acid | 4 |
| Magnesium stearate | 2 |
| Silicon dioxide | 5 |
| Amount to | 100 |
Agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight, mix homogeneously; It is an amount of to add wetting agent, and the system soft material is granulated drying; Granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight, stearic acid, silicon dioxide add in the granule, mix homogeneously in blender; Add the magnesium stearate mix homogeneously, tabletting, coating promptly gets.
Embodiment 5 (comparative example)
| Composition | Weight % |
| Agomelatine | 25 |
| Lactose | 43 |
| Starch | 17 |
| Carboxymethylstach sodium | 10 |
| Magnesium stearate | 5 |
| Amount to | 100 |
Agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight, mix homogeneously; It is an amount of to add wetting agent, and the system soft material is granulated drying; Granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight adds in the granule, mix homogeneously in blender; Add the magnesium stearate mix homogeneously, tabletting, coating promptly gets.
Embodiment 6
Dissolution determination
According to two appendix XC of 2005 editions Chinese Pharmacopoeias dissolution method, second method, measure the dissolution of above-mentioned 5 embodiment respectively, the result is following
By the write out a prescription dissolution (%) of sample of preparation of each embodiment
| Sampling time point | 0 | 10 | 20 | 30 | 45 | 60 |
| Embodiment 1 | 0 | 82.0 | 91.1 | 96.1 | 96.7 | 98.0 |
| Embodiment 2 | 0 | 80.8 | 91.4 | 95.1 | 96.6 | 98.1 |
| Embodiment 3 | 0 | 84.3 | 93.7 | 94.6 | 96.1 | 98.3 |
| Embodiment 4 | 0 | 84.7 | 91.2 | 94.8 | 96.1 | 98.8 |
| Embodiment 5 | 0 | 65.2 | 85.7 | 91.3 | 93.5 | 95.5 |
Comparing result can know that the dissolution of embodiment 1 to embodiment 4 obviously is superior to the dissolution of embodiment 5, and the inventive method can effectively improve the dissolubility of agomelatine tablet.
Embodiment 7
Pharmacokinetics is measured: human volunteer is carried out random packet, and per 5 volunteers take the tablet of preceding 5 embodiment.
Everyone was carried out agomelatine in 0,1,2,3,4,5,6,8,10,12,14,16 and 24 hour and detect taking the back; Write down the maximum plasma concentration (Cmax of this active component; Ng/ml); And blood drug level to the TG-AUC of time (AUC, ng.h/ml), the Cmax of each group and AUC value following.
| The Cmax ratio | The AUC ratio | |
| Embodiment 5 (comparative example) | 1 | 1 |
| Embodiment 1 | 4.5 | 3.8 |
| Embodiment 2 | 3.7 | 3.4 |
| Embodiment 3 | 3.5 | 3.3 |
| Embodiment 4 | 3.5 | 3.1 |
Comparing result can know that the inventive method can effectively improve the agomelatine tablet in the intravital bioavailability of people.
Claims (4)
1. a pharmaceutical composition that contains agomelatine is characterized in that being made up of following ingredients and percentage by weight: 11%～25% agomelatine, 30%～65% lactose, 11%～40% starch, 8%～15% carboxymethylstach sodium, 0.5%～5% stearic acid, 0.6%～2% magnesium stearate, 0.5%～5% silicon dioxide.
2. a kind of pharmaceutical composition that contains agomelatine according to claim 1 is characterized in that being made up of 16.67% agomelatine, 53.33% lactose, 15% starch, 10% carboxymethylstach sodium, 3% stearic acid, 1% magnesium stearate, 1% silicon dioxide.
3. a kind of pharmaceutical composition that contains agomelatine according to claim 1 and 2, the wherein preparation of preparation of pharmaceutical compositions.
4. a kind of pharmaceutical composition that contains agomelatine according to claim 4, wherein the method for preparing of preparation is: agomelatine is mixed with lactose, add the carboxymethylstach sodium of 1/2 weight, the starch of 2/3 weight; Mix homogeneously adds wetting agent, and the system soft material is granulated; Drying, granulate, with the carboxymethylstach sodium of 1/2 weight, the starch of 1/3 weight, stearic acid, silicon dioxide add in the granule; Mix homogeneously in blender adds the magnesium stearate mix homogeneously, tabletting, and coating promptly gets.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102458209A CN102342924A (en) | 2010-08-05 | 2010-08-05 | Medicine composition containing agomelatine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102458209A CN102342924A (en) | 2010-08-05 | 2010-08-05 | Medicine composition containing agomelatine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102342924A true CN102342924A (en) | 2012-02-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN2010102458209A Pending CN102342924A (en) | 2010-08-05 | 2010-08-05 | Medicine composition containing agomelatine |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104873470A (en) * | 2015-02-10 | 2015-09-02 | 济南利民制药有限责任公司 | Agomelatine tablet, film-coated tablet and preparation method thereof |
| CN105579065A (en) * | 2013-06-06 | 2016-05-11 | 赞蒂瓦有限合伙公司 | Agomelatine formulations comprising agomelatine in the form of co-crystals |
| CN106333929A (en) * | 2016-09-24 | 2017-01-18 | 万特制药(海南)有限公司 | Agomelatine-containing dispersible tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927205A (en) * | 2005-09-09 | 2007-03-14 | 瑟维尔实验室 | New association of agomelatine and a noradrenalin reuptake inhibitor, and pharmaceutical compositions containing them |
| CN101732296A (en) * | 2009-12-30 | 2010-06-16 | 北京德众万全药物技术开发有限公司 | Agomelatine-containing medicinal composition |
-
2010
- 2010-08-05 CN CN2010102458209A patent/CN102342924A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1927205A (en) * | 2005-09-09 | 2007-03-14 | 瑟维尔实验室 | New association of agomelatine and a noradrenalin reuptake inhibitor, and pharmaceutical compositions containing them |
| CN101732296A (en) * | 2009-12-30 | 2010-06-16 | 北京德众万全药物技术开发有限公司 | Agomelatine-containing medicinal composition |
Non-Patent Citations (1)
| Title |
|---|
| 徐祖砚等: "《药剂制造手册》", 30 September 1987, article "《粘合剂》", pages: 11 - 12 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105579065A (en) * | 2013-06-06 | 2016-05-11 | 赞蒂瓦有限合伙公司 | Agomelatine formulations comprising agomelatine in the form of co-crystals |
| JP2016520629A (en) * | 2013-06-06 | 2016-07-14 | ゼンティーバ，カー．エス． | Agomelatine formulation containing agomelatine in co-crystal form |
| CN105579065B (en) * | 2013-06-06 | 2018-11-16 | 赞蒂瓦有限合伙公司 | Agomelatine preparation comprising the agomelatine in co-crystal forms |
| CN104873470A (en) * | 2015-02-10 | 2015-09-02 | 济南利民制药有限责任公司 | Agomelatine tablet, film-coated tablet and preparation method thereof |
| CN106333929A (en) * | 2016-09-24 | 2017-01-18 | 万特制药(海南)有限公司 | Agomelatine-containing dispersible tablet and preparation method thereof |
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Application publication date: 20120208 |