CN102921008B - Stable drug composition containing calcium blockers - Google Patents
Stable drug composition containing calcium blockers Download PDFInfo
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- CN102921008B CN102921008B CN201210462072.9A CN201210462072A CN102921008B CN 102921008 B CN102921008 B CN 102921008B CN 201210462072 A CN201210462072 A CN 201210462072A CN 102921008 B CN102921008 B CN 102921008B
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- pharmaceutical composition
- azelnidipine
- calcium channel
- composition containing
- containing calcium
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Abstract
The invention relates to a stable drug composition containing calcium blockers. The stable drug composition is characterized in that the stable drug composition comprises (A) the calcium channel blockers, (B) an effective amount of alkaline excipients and (C) an effective amount of lipidic excipients. The drug composition disclosed by the invention has good storage stability and solves the problems of poor stability and short storage time of part of calcium channel blockers.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains Calcilytic, particularly a kind ofly can improve Calcilytic---the pharmaceutical composition of the stability of azelnidipine.
Background technology
Azelnidipine is that Japan three reaches the dihydropyridine type calcium antagonists that Ube Industries, Ltd develops altogether, on January 31st, 2003, in Japan, get the Green Light, list marketing in May in the same year, dosage form is tablet, trade name: Calblock, specification has two kinds: 8mg and 16mg.
Azelnidipine belongs to long-acting calcium antagonist, blood pressure lowering is mild and effect is lasting.In addition, azelnidipine may have a protective effect to artery is atherosis circumvascular gathering.Therefore, this medicine is subject to clinician and patient's attention day by day, is also constantly risen and consolidate in its market share.But, the pharmaceutical composition less stable of azelnidipine, extremely unstable to light, sour environment, high humidity and high temperature, and easily oxidation, be unfavorable for producing and storing.
Japan three altogether in patent application CN1436077A, once disclosed the stable pharmaceutical composition containing Calcilytic, disclosed the Stabilization that inorganic base and composition thereof plays in this pharmaceutical composition.The bright Kant's patent application of Shanghai medicine CN1762354A discloses the Stabilization that organic base EDTA slaine and composition thereof plays in this pharmaceutical composition.In the patent application CN101103979A of Hainan Sheng section, also once disclosed a kind of Azelnidipine medicinal composition and preparation method thereof, the Stabilization that wherein play-by-play organic base sodium acetate plays in this pharmaceutical composition.Although the three all considers the impact of pH on azelnidipine stability, its Stabilization to azelnidipine is not still very good.
Summary of the invention
The purpose of this invention is to provide a kind of stabilizing pharmaceutical composition that contains calcium channel blocker, the technical issues that need to address of the present invention are: improve the stability containing Azelnidipine composition.The present invention is directed to chemical property and the pharmaceutical composition thereof of Calcilytic azelnidipine, by further investigation, discovery adds alkaline matter and oil substances in pharmaceutical composition, can improve the stability containing Azelnidipine medicinal composition, has solved the stability problem of preparation in storing process.
Technical scheme of the present invention: the present invention relates to a kind of stabilizing pharmaceutical composition that contains Calcilytic (seeing following formula I), can be for oral.
Wherein, formula I is a kind of Calcilytic-azelnidipine.
The oil substances that the present composition comprises acceptable alkaline matter on the above-mentioned azelnidipine of the Calcilytic as effective ingredient and pharmacology and has antioxidation.
The weight of azelnidipine in pharmaceutical composition of the present invention (I) is generally the 1%-30% of total formulation weight amount, preferably 2%-10%.
The present invention is in order to obtain the stabilizing pharmaceutical composition that contains Calcilytic (I), and as being used for treating hypertensive purpose, research through deep, found that and add alkaline matter and oil substances in pharmaceutical composition, but synergism improves the stability of pharmaceutical composition.
Used in the present invention to make the alkaline matter that pharmaceutical composition plays Stabilization be meglumine, and its addition accounts for 0.1～20% of total formulation weight amount, preferably 1～15%.
The oil substances that pharmaceutical composition is played to Stabilization used in the present invention is Glyceryl Behenate, glyceryl palmitostearate, stearic acid, glyceryl monostearate, hydrogenated vegetable oil, the mixture of one or more in castor oil hydrogenated, its addition accounts for 0.1～20% of total formulation weight amount.
Pharmaceutical composition of the present invention can adopt various pharmaceutical dosage forms, and representational is tablet, capsule etc., technique preparation routinely.As tablet can be used dry granulation, wet granulation or direct powder compression; Capsule technique routinely directly is filled into granule or mixed-powder in capsule and manufactures.
Manufacture pharmaceutical composition of the present invention, also can optionally use the adjuvant that is applicable to each preparation, as filler, binding agent, disintegrating agent, surfactant, lubricant etc.These adjuvants are so long as normally used adjuvant on galenic pharmacy, and the azelnidipine above-mentioned formula (I) not meaned and the stability of pharmaceutical composition produce harmful effect and do not get final product.
Filler can be cellulose or the cellulose derivative classes such as microcrystalline Cellulose, as various starch, and dextrin and starch derivatives; Mannitol, sugar alcohols or the saccharides such as lactose; Calcium sulfate, the inorganic salts such as calcium hydrogen phosphate.
Binding agent can be water, alcoholic solution, HPMC, HPC, PVP, EC, MC etc.
Disintegrating agent can be carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose and their mixture etc.
Surfactant can be tween, poloxamer, sodium lauryl sulphate etc.
Lubricant can be magnesium stearate, micropowder silica gel, Pulvis Talci, Magnesiumaluminumsilicate etc.
The kind of above adjuvant used is different and different according to the dosage form of industrial pharmacy with consumption, can be according to the selection that needs of preparation technique.
Useful result of the present invention is: by the present invention, can obtain the stabilizing pharmaceutical composition that contains Calcilytic azelnidipine, alkaline matter and oil substances, the preparation that contains such pharmaceutical composition has stability preferably.
The specific embodiment
Following examples can contribute to understand the present invention, do not limit to the following example content but content of the present invention comprises.
Embodiment 1
Tablet 1:(table 1):
Preparation process: the recipe quantity azelnidipine was mixed to 60 mesh sieves with a part of vertical compression mannitol, then add residue prescription mannitol, low-substituted hydroxypropyl cellulose, meglumine, hydrogenated vegetable oil, micropowder silica gel mixed 60 mesh sieves, finally added recipe quantity magnesium stearate mix homogeneously.Be the shallow circular arc stamping of 7.5mm with diameter again, obtain the azelnidipine sheet.
Said preparation, at 75prm, is measured to the 45min dissolution in 0.1M hydrochloric acid, dissolution is 99.8%.
Synchronously according to embodiment 1 formula preparation, do not add in addition the Azelnidipine tablets (comparative example 1-1) of meglumine and hydrogenated vegetable oil.
Embodiment 2
Capsule 1:
According to above-described embodiment 1 prescription, with the direct fill process of powder, by the mixed-powder obtained in the upper example 3# capsule of packing into.Said preparation, at 75prm, is measured to the 45min dissolution in 0.1M hydrochloric acid, dissolution is 99.5%.
Embodiment 3
Tablet 2:(table 2)
Preparation process: by recipe quantity azelnidipine and mannitol, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, meglumine is mix homogeneously in the efficient wet mixer, then adds 5%HPMC water liquid to stir soft material processed, with 20 order stainless steel meshs, sieves, and makes wet granular; Wet granular is put into to 60 ℃ of ventilation freeze-day with constant temperature baking ovens dry, 20 mesh sieve granulate after drying add micropowder silica gel simultaneously, hydrogenated vegetable oil, and the magnesium stearate mix homogeneously obtains the dry granule of azelnidipine.Be the shallow circular arc stamping of 7.5mm with diameter again, obtain the azelnidipine sheet.
Said preparation, at 75prm, is measured to the 45min dissolution in 0.1M hydrochloric acid, dissolution is 99.2%.
Embodiment 4
Capsule 2
According to above-described embodiment 3 prescription, with the direct fill process of powder, by the mixed-powder obtained in the upper example 3# capsule of packing into.Said preparation, at 75prm, is measured to the 45min dissolution in 0.1M hydrochloric acid, dissolution is 99.2%.
Embodiment 4
Method gained tablet and comparative example 1-1, the common former method gained tablet that grinds sheet, CN1762354A embodiment 1 and CN1762354A embodiment 1 of Japan three with the embodiment of the present invention 1 carry out stability data relatively under the condition of 60 ℃ of high temperature and high humidity 75%RH.
60 ℃ of stability test results of table 3 high temperature
Table 4 high humidity 75%RH stability test result
The conclusion embodiment of the present invention is all compared than embodiment 1-1, former triturate, and the preparation of CN1762354A embodiment 1 and CN1762354A embodiment 1 is good at 60 ℃ of high temperature and high humidity 75% condition stability inferior.
Claims (4)
1. the stabilizing pharmaceutical composition containing calcium channel blocker is characterized in that comprising:
(A) calcium channel blocker;
(B) basic auxiliary of effective dose;
(C) the oils adjuvant of effective dose;
Wherein said calcium channel blocker is azelnidipine, and it is the unique active component in compositions; Described basic auxiliary is meglumine, and the meglumine addition accounts for 0.1～20% of pharmaceutical composition total amount; Described oils adjuvant is Glyceryl Behenate, glyceryl palmitostearate, and glyceryl monostearate, hydrogenated vegetable oil, the mixture of one or more in castor oil hydrogenated, its addition accounts for 0.1～20% of pharmaceutical composition total amount.
2. a kind of stabilizing pharmaceutical composition containing calcium channel blocker according to claim 1, is characterized in that, the azelnidipine consumption accounts for 1～30% of pharmaceutical composition total amount.
3. a kind of stabilizing pharmaceutical composition containing calcium channel blocker according to claim 2, is characterized in that, the azelnidipine consumption accounts for 2～10% of pharmaceutical composition total amount.
4. a kind of stabilizing pharmaceutical composition containing calcium channel blocker according to claim 1, is characterized in that, the meglumine addition accounts for 1～15% of pharmaceutical composition total amount.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210462072.9A CN102921008B (en) | 2012-11-16 | 2012-11-16 | Stable drug composition containing calcium blockers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210462072.9A CN102921008B (en) | 2012-11-16 | 2012-11-16 | Stable drug composition containing calcium blockers |
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| CN102921008A CN102921008A (en) | 2013-02-13 |
| CN102921008B true CN102921008B (en) | 2014-01-01 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473888B (en) * | 2014-11-20 | 2017-01-18 | 南京正大天晴制药有限公司 | Pharmaceutical composition of azelnidipine |
| CN108186589B (en) * | 2018-03-26 | 2020-08-07 | 迪沙药业集团有限公司 | Azelnidipine composition |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1436077A (en) * | 2000-04-11 | 2003-08-13 | 三共株式会社 | Stabilized pharmaceutical compositions contg. calcium channel blockers |
| CN1762354A (en) * | 2004-10-18 | 2006-04-26 | 上海药明康德新药开发有限公司 | Stable pharmaceutical composition containing calcium blocker |
| CN101103979A (en) * | 2006-07-14 | 2008-01-16 | 海南盛科生命科学研究院 | Azelnidipine medicinal composition and its preparing method |
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2012
- 2012-11-16 CN CN201210462072.9A patent/CN102921008B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1436077A (en) * | 2000-04-11 | 2003-08-13 | 三共株式会社 | Stabilized pharmaceutical compositions contg. calcium channel blockers |
| CN1762354A (en) * | 2004-10-18 | 2006-04-26 | 上海药明康德新药开发有限公司 | Stable pharmaceutical composition containing calcium blocker |
| CN101103979A (en) * | 2006-07-14 | 2008-01-16 | 海南盛科生命科学研究院 | Azelnidipine medicinal composition and its preparing method |
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