CN102357095A - Stable medicinal composition - Google Patents
Stable medicinal composition Download PDFInfo
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- CN102357095A CN102357095A CN2011102039750A CN201110203975A CN102357095A CN 102357095 A CN102357095 A CN 102357095A CN 2011102039750 A CN2011102039750 A CN 2011102039750A CN 201110203975 A CN201110203975 A CN 201110203975A CN 102357095 A CN102357095 A CN 102357095A
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- candesartan cilexetil
- polyethylene glycol
- coating
- candesartan
- preparation
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Abstract
The invention relates to a candesartan cilexetil composition, which comprises a candesartan cilexetil coating coated by polyethylene glycol 6000, wherein the coating can be mixed with the common medicinal auxiliary materials. The candesartan cilexetil composition is prepared by technologies of dry-method granulation and tabletting, so the problem that candesartan cilexetil is easy to decompose in the preparation process is solved.
Description
Technical field: the present invention relates to a kind of stable candesartan Cilexetil pharmaceutical composition.
Background technology: candesartan Cilexetil is the antihypertensive drugs of Japanese Wu Tian company research and development; Chemical name: (±)-1-[[(hexamethylene oxo) carbonyl] oxo] ethyl 2-ethyoxyl-1-[[2 '-(1H-tetrazole base-5)-[1,1 '-xenyl]-4-yl] methyl]-1H-benzimidazole-7-carboxylate.Molecular formula: C
33H
34N
6O
6, molecular weight: 610.66, be used to treat essential hypertension.
Candesartan Cilexetil is white or off-white color crystalline powder, is dissolved in methanol, and is water insoluble.The solid-state independent placement of these article is all stablized temperature, steam and light, but after processing composition tablet by conventional method, and its active component content is and progressively reduces trend, and impurity is progressively ascendant trend.Chinese patent CN1047518C; CN1044088C discloses candesartan Cilexetil and fusing point greatly about 20-90 ℃ the oiliness compound compositions that forms of Polyethylene Glycol particularly; Its preparation method is that the oiliness compound of the fusing point that comprises Polyethylene Glycol at 20-90 ℃ mixed with adjuvant commonly used; Wet granulation is processed conventional tablet by conventional method then.
Summary of the invention
Goal of the invention: for the patient provides a kind of stable, reliable pharmaceutical composition.Solve candesartan Cilexetil stability of formulation problem.
The technical problem that the present invention will solve: handle through certain process, obtain a kind of candesartan Cilexetil coating by coated with polyethylene glycol, this coating can mix with common medicinal supplementary material, prepares the Candesartan ester composition with common preparation technique.
For realizing above-mentioned purpose, the applicant has carried out a series of experiment, experiment showed, candesartan Cilexetil is scattered in the ethanol water of polyethylene glycol 6000, stirs filtration, oven drying at low temperature.Resulting material adopts common preparation technique just can obtain highly stable candesartan Cilexetil tablet.
Technical scheme of the present invention is:
A kind of Candesartan ester composition is characterized in that containing the candesartan Cilexetil coating that is coated by polyethylene glycol 6000.
Compositions of the present invention, wherein by the content of candesartan Cilexetil in the candesartan Cilexetil coating of coated with polyethylene glycol 85---between 96%, preparation of compositions method according to the invention is characterized in that:
The first step prepares the alcoholic solution of polyethylene glycol 6000.
Ethanol is mixed with water, add polyethylene glycol 6000,35 ℃ of-45 ℃ of stirring and dissolving.
The polyethylene glycol 6000 that this step is suitable, water, alcoholic acid mass ratio are 1: (1～3): in (3～8) scope.
This step optimized technical scheme is polyethylene glycol 6000 1 gram, water 1 gram, ethanol 3 grams, 40 ℃ of stirring and dissolving.
This step optimized technical scheme is polyethylene glycol 6000 1 gram, water 2 grams, ethanol 4 grams.
This step optimized technical scheme is polyethylene glycol 6000 1 gram, water 2 grams, ethanol 8 grams.
The candesartan Cilexetil coating that the preparation of second step is coated by polyethylene glycol 6000.
Candesartan Cilexetil is scattered in the first step gained solution, and stirring lets it fully disperse.Room temperature is filtered, and oven drying at low temperature is measured Candesartan ester content wherein.
The candesartan Cilexetil that this step suits is 1 with the solution quality ratio of the first step: (1～3).
This step optimized technical scheme is a candesartan Cilexetil and the solution quality ratio of the first step is 1: (1～2.5)
This step optimized technical scheme is that 30 gram candesartan Cilexetils are scattered in the solution of 30 gram first step preparations.
This step optimized technical scheme is that 30 gram candesartan Cilexetils are scattered in the solution of 45 gram first step preparations.
The bake out temperature that this step is suitable is 38 ℃～42 ℃.
The 3rd step prepared the Candesartan ester composition by common preparation technique.
Preparation of compositions method according to the invention, optimized technical scheme are to adopt dry granulation, tabletting.
The invention has the beneficial effects as follows:, obtained the highly stable candesartan Cilexetil coating of performance through PROCESS FOR TREATMENT of the present invention.This material uses dry granulation, tabletting.Resulting tablet stability is better.
Embodiment 1,
The first step is by the preparation of the candesartan Cilexetil coating of polyethylene glycol 6000 coating
1 gram water and 3 gram ethanol are dissolved each other, add 2.0 gram polyethylene glycol 6000s, 40 ℃ of stirring and dissolving.Candesartan Cilexetil 5 gram is added wherein, stir and let it fully disperse in 6 hours.Filter, 38 ℃～42 ℃ oven dry gains, the Candesartan ester content of measuring wherein is 88.6%.
The second step preparation of compositions:
Take by weighing the candesartan Cilexetil coating that is equivalent to candesartan Cilexetil 1mg, lactose 93mg, corn starch 20.0mg by the polyethylene glycol 6000 coating; Hydroxypropyl cellulose 4.0mg, water is an amount of, presses the pharmaceutical industry conventional method and granulates; 40 ℃ of oven dry; Add carboxymethylcellulose calcium 5.6mg again, magnesium stearate 0.4mg presses pharmaceutical industry conventional method tabletting.
Embodiment 2
The first step is by the preparation of the candesartan Cilexetil coating of polyethylene glycol 6000 coating
2.5 gram water and 7.5 gram ethanol are dissolved each other, add 2.5 gram polyethylene glycol 6000s, 35 ℃ of stirring and dissolving.Candesartan Cilexetil 5 gram is added wherein, stir and let it fully disperse in 6 hours.Filter, 38～42 ℃ of oven dry gains, the Candesartan ester content of measuring wherein is 85.2%.
The second step preparation of compositions:
Take by weighing the candesartan Cilexetil coating that is equivalent to candesartan Cilexetil 1mg by the polyethylene glycol 6000 coating, lactose 93mg, pregelatinized Starch 30.0mg, hydroxypropyl cellulose 4.0mg granulates tabletting.
Embodiment 3
The first step is by the preparation of the candesartan Cilexetil coating of polyethylene glycol 6000 coating
1 gram water and 3.5 gram ethanol are dissolved each other, add 1.5 gram polyethylene glycol 6000s, 45 ℃ of stirring and dissolving.Candesartan Cilexetil 5 gram is added wherein, stir and let it fully disperse in 5 hours.Filter, 38 ℃～42 ℃ oven dry gains, the Candesartan ester content of measuring wherein is 90.82%.
The second step preparation of compositions:
Take by weighing the candesartan Cilexetil coating that is equivalent to candesartan Cilexetil 1mg, lactose 93mg, pregelatinized Starch 30.0mg by the polyethylene glycol 6000 coating; Hydroxypropyl cellulose 4.0mg, dry granulation adds carboxymethylcellulose calcium 5.6mg again; Magnesium stearate 0.4mg, tabletting.
Embodiment 4
The first step is by the preparation of the candesartan Cilexetil coating of polyethylene glycol 6000 coating
2 gram water and 8 gram ethanol are dissolved each other, add 1 gram polyethylene glycol 6000,38 ℃～42 ℃ stirring and dissolving.Candesartan Cilexetil 5 gram is added wherein, stir and let it fully disperse in 4～6 hours.Filter, 38 ℃～42 ℃ oven dry gains, the Candesartan ester content of measuring wherein is 96.3%.
The second step preparation of compositions:
Take by weighing and be equivalent to the candesartan Cilexetil coating that candesartan Cilexetil 1mg is coated by polyethylene glycol 6000, lactose 93mg, pregelatinized Starch 30.0mg, hydroxypropyl cellulose 4.0mg, dry granulation, tabletting.
Reference examples 1 (the disclosed prescription of CN1047518C)
Prescription: candesartan Cilexetil 1mg, lactose 93.0mg, corn starch 20.0mg, polyethylene glycol 6000 6.0mg, hydroxypropyl cellulose 4.0mg, water is an amount of, carboxymethylcellulose calcium 5.6mg, magnesium stearate 0.4mg.
Candesartan Cilexetil, lactose, corn starch, polyethylene glycol 6000 are mixed, on mixture, spray hydroxypropyl cellulose aqueous solution as binding agent,, through granulating 40 ℃ of dryings.Add carboxymethylcellulose calcium and magnesium stearate, tabletting.
Reference examples 2
Must write out a prescription by reference examples 1; Candesartan Cilexetil is dispersed in the aqueous solution of hydroxypropyl methylcellulose of polyethylene glycol 6000, this dispersion liquid is added in the pulverulent mixture of lactose and corn starch, then through granulating and drying obtains granule; Add carboxymethylcellulose calcium and magnesium stearate, tabletting.
With 40 ℃ in embodiment 1～4 sample and reference examples 1～2 sample, under relative humidity 70% situation, deposited 70 days. measure each sample candesartan Cilexetil content and its related substances, data record is in table 1.
Table 1, product stability of the present invention are investigated result of the test
For pharmaceutical preparation, the decline of product active component content influences curative effect of medication; Increasing of related substance influences the safety of medicine.Data can draw from table, and product of the present invention is at 40 ℃, under relative humidity 70% situation, deposit 70 days after, the candesartan Cilexetil changes of contents amplitude in the compositions is less than reference examples, the increasing degree of related substance is also less than reference examples.The stability of the experiment proof present composition has greatly improved with respect to prior art.
Claims (7)
1. a Candesartan ester composition is characterized in that containing the candesartan Cilexetil coating that polyethylene glycol 6000 coats.
2. the described compositions of claim 1, wherein by the content of candesartan Cilexetil in the candesartan Cilexetil coating of coated with polyethylene glycol between 85%～96%.
3. the said preparation of compositions method of claim 1 is characterized in that:
The first step is with Polyethylene Glycol, water, ethanol stirring and dissolving by a certain percentage;
Second step dissolved candesartan Cilexetil and is scattered in the first step solution, and preparation is by the candesartan Cilexetil coating of coated with polyethylene glycol;
The 3rd step prepared the Candesartan ester composition by common preparation technique.
4. claim 3 described method for preparinies is characterized in that first step polyethylene glycol 6000, water, alcoholic acid mass ratio are 1: (1～3): in (3～8) scope, and 35 ℃ of 45 ℃ of stirring and dissolving.
5. claim 3 or 4 described method for preparinies is characterized in that first step polyethylene glycol 6000, water, alcoholic acid mass ratio are 1: (1～3): in (3～8) scope, and 40 ℃ of stirring and dissolving
6. claim 3 described method for preparinies is characterized in that the second step candesartan Cilexetil and the solution quality ratio of the first step are 1: (1～3).
7. the said preparation of compositions method of claim 1 is characterized in that dry granulation, tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102039750A CN102357095A (en) | 2011-07-12 | 2011-07-12 | Stable medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102039750A CN102357095A (en) | 2011-07-12 | 2011-07-12 | Stable medicinal composition |
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| CN102357095A true CN102357095A (en) | 2012-02-22 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2011102039750A Pending CN102357095A (en) | 2011-07-12 | 2011-07-12 | Stable medicinal composition |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110354086A (en) * | 2019-07-25 | 2019-10-22 | 天地恒一制药股份有限公司 | A kind of preparation method of candesartan Cilexetil tablet |
| CN112957336A (en) * | 2021-03-03 | 2021-06-15 | 广州白云山天心制药股份有限公司 | Stable candesartan cilexetil medicinal solid composition and preparation method thereof |
| CN117442577A (en) * | 2023-12-21 | 2024-01-26 | 山东则正医药技术有限公司 | Candesartan cilexetil microchip and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1072338A (en) * | 1991-11-20 | 1993-05-26 | 武田药品工业株式会社 | Combination of oral medication and preparation method |
-
2011
- 2011-07-12 CN CN2011102039750A patent/CN102357095A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1072338A (en) * | 1991-11-20 | 1993-05-26 | 武田药品工业株式会社 | Combination of oral medication and preparation method |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110354086A (en) * | 2019-07-25 | 2019-10-22 | 天地恒一制药股份有限公司 | A kind of preparation method of candesartan Cilexetil tablet |
| CN110354086B (en) * | 2019-07-25 | 2021-05-11 | 天地恒一制药股份有限公司 | Preparation method of candesartan cilexetil tablets |
| CN112957336A (en) * | 2021-03-03 | 2021-06-15 | 广州白云山天心制药股份有限公司 | Stable candesartan cilexetil medicinal solid composition and preparation method thereof |
| CN117442577A (en) * | 2023-12-21 | 2024-01-26 | 山东则正医药技术有限公司 | Candesartan cilexetil microchip and preparation method and application thereof |
| CN117442577B (en) * | 2023-12-21 | 2024-03-15 | 山东则正医药技术有限公司 | Candesartan cilexetil microchip and preparation method and application thereof |
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Effective date of registration: 20140926 Address after: 264200 No. 1 South Qingdao Road, Weihai economic and technological development, Shandong Applicant after: Disha Pharmaceutical Industry Group Corp., Ltd. Applicant after: Weihai Disu Pharmaceutical Co., Ltd. Address before: 264200 No. 1 South Qingdao Road, Weihai economic and technological development, Shandong Applicant before: Disha Pharmaceutical Industry Group Corp., Ltd. Applicant before: Disha Pharmaceutical Group Shandong Disha Pharmaceutical Co., Ltd. Applicant before: Weihai Disu Pharmaceutical Co., Ltd. |
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Application publication date: 20120222 |