CN105125539A - Pioglitazone metformin tablet and preparation method thereof - Google Patents
Pioglitazone metformin tablet and preparation method thereof Download PDFInfo
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- CN105125539A CN105125539A CN201510473300.6A CN201510473300A CN105125539A CN 105125539 A CN105125539 A CN 105125539A CN 201510473300 A CN201510473300 A CN 201510473300A CN 105125539 A CN105125539 A CN 105125539A
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- pioglitazone
- metformin hydrochloride
- hydrochloride
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Abstract
The invention discloses a pioglitazone metformin tablet and a preparation method thereof. The tablet comprises metformin hydrochloride particles, pioglitazone hydrochloride and pharmaceutically acceptable auxiliary materials. The metformin hydrochloride particles are obtained by pelletizing single metformin hydrochloride or a combination of the metformin hydrochloride and the pharmaceutically acceptable auxiliary materials. The obtained tablet can dissolve rapidly, content uniformity is high, preparation steps are simple, and industrial production is benefited.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to pioglitazone diformin tablet and preparation method thereof.
Background technology
The sickness rate of diabetes continues to rise, and has become one of 5 kinds of the highest diseases of whole world M & M, especially increases more remarkable with China, a print developing country such as subcontinent and Africa.Diabetes can be divided into 1 type, i.e. insulin-dependent diabetes (IDDM) and 2 types, i.e. noninsulindependent diabetes (NIDDM) amphitypy.In the diabetics quantitatively sharply increased, NIDDM at least accounts for patient populations's more than 90%.NIDDM medicine comprises sulfonylurea, biguanides, alpha-glucosaccharase enzyme inhibitor, Insulin sensitizing drugs and mealtime blood sugar regulating etc.
Insulin sensitizing drugs can improve the mechanism of insulin resistant and blood sugar lowering and competitive peroxide activator enzyme paraphyte receptor y (PPAR γ), regulates transcribing of Insulin sensitivity gene relevant.Pioglitazone is thiazolidinediones antidiabetic medicine, is a para-insulin enhanced sensitivity medicine, can improves islet beta cell function, significantly improve insulin resistant and related metabolic disturbance, all have obvious curative effects to type 2 diabetes mellitus and cardiovascular complication thereof.Pharmaceutical salts comprises pioglitazone hydrochloride, and structural formula is as follows:
Metformin is mainly used in mild diabetics, is particularly useful for fat and alone diet control nonresponder.Pharmaceutical salts comprises metformin hydrochloride, and structural formula is as follows:
The use in conjunction of pioglitazone hydrochloride and metformin hydrochloride, can more effective control blood glucose, and can reduce the incidence rate etc. of untoward reaction.This compound preparation develops listing by Japan's military field pharmacy, and specification has 15/500mg and 15/850mg, and commodity are called
aCTOPLUSMET.
Patent CN03816478.7 discloses a kind of preparation method of coated preparation, comprises and uses pioglitazone hydrochloride dispersion liquid in organic solvent to carry out coating to improve the dissolution of pioglitazone hydrochloride to metformin hydrochloride tablet core.But the pioglitazone diformin tablet that this technology provides adopts organic solvent in preparation process, higher to the requirement of equipment, is also unfavorable for environmental conservation.
Patent CN200380104419.1 discloses the pioglitazone hydrochloride of certain particle diameter and the solid preparation of metformin hydrochloride composition.The pioglitazone hydrochloride of fine grain is granulated by this technology together with metformin hydrochloride in fluid bed.The pioglitazone hydrochloride of fine grain, exists and is blown away in fluid bed, or sticks to equipment surface, causes the on the low side or underproof risk of uniformity of dosage units of its content.
Summary of the invention
Pioglitazone diformin tablet provided by the invention, be made up of metformin hydrochloride granule and pioglitazone hydrochloride and pharmaceutically acceptable adjuvant, wherein said metformin hydrochloride granule obtains after the independent or pharmaceutically acceptable adjuvant of metformin hydrochloride is granulated together.
The method of granulating of described metformin hydrochloride granule can be selected from wet granulation technology or dry granulation etc., preferred wet granulation technology; Binding agent is more preferably made into granulation solution by metformin hydrochloride granule, adopts fluidized bed granulation technique to granulate to metformin hydrochloride, and obtain through the granulate that sieves.
For ensureing the compressibility of granule and the mixing homogeneity of two kinds of active component, wherein particle diameter D90≤200 μm of metformin hydrochloride before granulation, preferred D90≤150 μm, preferred D90≤90 μm.
Above-mentioned particle diameter is measured by laser particle analyzer Mastersiezer2000, and represents with the form of particle volume diameter.In cumulative distribution, the particle footpath of accumulated value just in time corresponding to 90%, is D90.The experiment parameter of droplet measurement is as follows:
Refraction coefficient: 1.50; Absorptance: 0.1; Sample injection disc slit width: 10mm; Analytical model: universal; Measuring Time: 12s; Background Measuring Time: 12s; Air pressure: 0.5bar; Concussion sample rate: 50%; Shading rate scope 0.5%-6%;
With the air of 4.0bar pressure, instrument pipeline is cleaned, by above optimum configurations instrument, get about 1-2g sample and place in sample injection disc, start instrument and automatically detect.
Described pharmaceutically acceptable adjuvant be selected from filler, disintegrating agent, binding agent, lubricant one or more:
Wherein filler is selected from one or more in microcrystalline Cellulose, optimization microcrystalline Cellulose, calcium hydrogen phosphate;
Wherein disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, low-substituted hydroxypropyl cellulose;
Wherein binding agent be selected from hyprolose, polyvidone, hypromellose one or more;
Wherein lubricant is selected from one or more in magnesium stearate, calcium stearate, Glyceryl Behenate, sodium stearyl fumarate, silicon dioxide, colloidal silica, polyethylene glycol 6000, Pulvis Talci.
Preferred each component account for total tablet anharmonic ratio such as under:
Pioglitazone diformin tablet of the present invention, is wherein equivalent to pioglitazone 15mg containing pioglitazone hydrochloride 16.53mg(), containing metformin hydrochloride 500mg or 850mg.
Pioglitazone diformin tablet of the present invention, when metformin hydrochloride granule adopts fluidized bed granulation technique to prepare, comprises the steps:
A. binding agent is made into granulation solution, adopts fluidized bed granulation technique to granulate to metformin hydrochloride;
B. the material in step a is sieved granulate, obtain the metformin hydrochloride granule of suitable particle size;
C. pioglitazone hydrochloride is sieved with pharmaceutically acceptable adjuvant and mix;
D. the metformin hydrochloride granule of step b gained is carried out sieving mixing with the mixture of step c gained, then with mix lubricant;
E. tabletting is carried out to steps d, obtain pioglitazone diformin tablet.
Wherein the mixing of sieving of step c and d can be once, also can be that repeated mixing is sieved.
The mobility of metformin hydrochloride own and compressibility all poor, the present invention by first preparing metformin hydrochloride granule, makes its mobility and compressibility improve, is conducive to the carrying out of tableting step technique below.The pioglitazone diformin tablet that the present invention obtains can Fast Stripping and uniformity of dosage units good, and preparation process is simple, is conducive to suitability for industrialized production.
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be further described, but embodiment is not limited to the present invention.
embodiment 1-2
The particle diameter D90=205 μm of metformin hydrochloride.
Preparation method is as follows:
Binding agent polyvidone purified water is mixed with 20%(w/w) solution.Metformin hydrochloride is placed in fluid bed, granulates with binder solution, drying after hydrojet completes, and material is carried out sieving granulate, obtains metformin hydrochloride granule.Detect the metformin hydrochloride granule of embodiment 1 and 2 is respectively 32 ° and 36 ° angle of repose.
After pioglitazone hydrochloride, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose sieve together, mix in total mixed bucket, 3 times like this.Mix with metformin hydrochloride pellet through sieves again, 3 times like this.Finally add magnesium stearate lubricant mixing, obtain mixed granule.
The mixed granule obtained is pressed into tablet.
The tablet obtained is carried out coating.
embodiment 3
The particle diameter D90=144 μm of metformin hydrochloride.
Preparation method is as follows:
Binding agent hydroxypropyl cellulose purified water is mixed with 5%(w/w) solution.Metformin hydrochloride is placed in fluid bed, granulates with binder solution, drying after hydrojet completes, and material is carried out sieving granulate, obtains metformin hydrochloride granule, detects its angle of repose is 30 °
After pioglitazone hydrochloride, microcrystalline Cellulose, carboxymethylcellulose calcium, cross-linking sodium carboxymethyl cellulose sieve together, mix in total mixed bucket, 3 times like this.Mix with metformin hydrochloride pellet through sieves again, 2 times like this.Finally add magnesium stearate lubricant mixing, obtain mixed granule.
The mixed granule obtained is pressed into tablet.
The tablet obtained is carried out coating.
embodiment 4
The particle diameter D90=65 μm of metformin hydrochloride.
Preparation method is as follows:
Binding agent polyvidone purified water is mixed with 20%(w/w) solution.Metformin hydrochloride mixes with colloidal silica and is placed in fluid bed, and granulate with binder solution, drying after hydrojet completes, carries out sieving granulate by material, obtains metformin hydrochloride granule, detects its angle of repose is 40 °.
After pioglitazone hydrochloride, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose sieve together, mix in total mixed bucket.Mix with metformin hydrochloride pellet through sieves again.Finally add magnesium stearate lubricant mixing, obtain mixed granule.
The mixed granule obtained is pressed into tablet.
The tablet obtained is carried out coating.
embodiment 5
The particle diameter D90=65 μm of metformin hydrochloride.
Preparation method is as follows:
Binding agent polyvidone purified water is mixed with 20%(w/w) solution.Metformin hydrochloride is placed in fluid bed, granulates with binder solution, drying after hydrojet completes, and material is carried out sieving granulate, obtains metformin hydrochloride granule, detects its angle of repose is 38 °.
After pioglitazone hydrochloride, microcrystalline Cellulose, calcium hydrogen phosphate, cross-linking sodium carboxymethyl cellulose sieve together, mix in total mixed bucket.Mix with metformin hydrochloride pellet through sieves again.Finally add magnesium stearate lubricant mixing, obtain mixed granule.
The mixed granule obtained is pressed into tablet.
The tablet obtained is carried out coating.
embodiment 6
Dissolution detection method is 37 ± 0.5 DEG C, paddle method (II method) 50rpm, Mcllvaine buffer solution (pH2.5), 900ml.
Embodiment 1 ~ 5 coated tablet dissolution testing result is as follows:
embodiment 7
In embodiment 1 ~ 5 coated tablet, pioglitazone uniformity of dosage units testing result is as follows:
Claims (11)
1. a pioglitazone diformin tablet, it is characterized in that being made up of metformin hydrochloride granule and pioglitazone hydrochloride and pharmaceutically acceptable adjuvant, wherein said metformin hydrochloride granule be metformin hydrochloride separately or obtain after granulating together with pharmaceutically acceptable adjuvant.
2. pioglitazone diformin tablet according to claim 1, wherein said metformin hydrochloride granule is that binding agent is made into granulation solution, adopts fluidized bed granulation technique to granulate to metformin hydrochloride, and obtain through the granulate that sieves.
3. pioglitazone diformin tablet according to claim 1, wherein particle diameter D90≤200 μm of metformin hydrochloride before granulation, preferred D90≤150 μm, preferred D90≤90 μm.
4. pioglitazone diformin tablet according to claim 1, wherein said pharmaceutically acceptable adjuvant be selected from filler, disintegrating agent, binding agent, lubricant one or more.
5. pioglitazone diformin tablet according to claim 4, each component account for total tablet anharmonic ratio such as under.
6. pioglitazone diformin tablet according to claim 4, wherein filler is selected from one or more in microcrystalline Cellulose, optimization microcrystalline Cellulose, calcium hydrogen phosphate.
7. pioglitazone diformin tablet according to claim 4, wherein disintegrating agent is selected from one or more in cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, low-substituted hydroxypropyl cellulose.
8. pioglitazone diformin tablet according to claim 4, wherein binding agent be selected from hyprolose, polyvidone, hypromellose one or more.
9. pioglitazone diformin tablet according to claim 4, wherein lubricant is selected from one or more in magnesium stearate, calcium stearate, Glyceryl Behenate, sodium stearyl fumarate, silicon dioxide, colloidal silica, polyethylene glycol 6000, Pulvis Talci.
10. pioglitazone diformin tablet according to claim 1, wherein containing pioglitazone hydrochloride 16.53mg, containing metformin hydrochloride 500mg or 850mg.
The preparation method of 11. pioglitazone diformin tablets according to claim 2, comprises the steps:
A. binding agent is made into granulation solution, adopts fluidized bed granulation technique to granulate to metformin hydrochloride;
B. the material in step a is sieved granulate, obtain the metformin hydrochloride granule of suitable particle size;
C. pioglitazone hydrochloride is sieved with pharmaceutically acceptable adjuvant and mix;
D. the metformin hydrochloride granule of step b gained is carried out sieving mixing with the mixture of step c gained, then with mix lubricant;
E. tabletting is carried out to steps d, obtain pioglitazone diformin tablet.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510473300.6A CN105125539A (en) | 2015-08-05 | 2015-08-05 | Pioglitazone metformin tablet and preparation method thereof |
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| CN201510473300.6A CN105125539A (en) | 2015-08-05 | 2015-08-05 | Pioglitazone metformin tablet and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107536831A (en) * | 2016-06-29 | 2018-01-05 | 深圳翰宇药业股份有限公司 | A kind of composition and preparation method containing vildagliptin and melbine |
| US20190184055A1 (en) * | 2016-07-12 | 2019-06-20 | Urgo Recherche Innovation Et Developpement | Dressing Enabling the Controlled and Prolonged Release of Metformin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1582928A (en) * | 2004-06-08 | 2005-02-23 | 天津药物研究院 | Medicinal composition and its use in treatment of diabetes |
| CN1717253A (en) * | 2002-10-07 | 2006-01-04 | 武田药品工业株式会社 | Solid preparation |
-
2015
- 2015-08-05 CN CN201510473300.6A patent/CN105125539A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1717253A (en) * | 2002-10-07 | 2006-01-04 | 武田药品工业株式会社 | Solid preparation |
| CN1582928A (en) * | 2004-06-08 | 2005-02-23 | 天津药物研究院 | Medicinal composition and its use in treatment of diabetes |
Non-Patent Citations (1)
| Title |
|---|
| 杨基森: "《中药制剂设计学》", 31 March 1992, 贵州科技出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107536831A (en) * | 2016-06-29 | 2018-01-05 | 深圳翰宇药业股份有限公司 | A kind of composition and preparation method containing vildagliptin and melbine |
| US20190184055A1 (en) * | 2016-07-12 | 2019-06-20 | Urgo Recherche Innovation Et Developpement | Dressing Enabling the Controlled and Prolonged Release of Metformin |
| US11191866B2 (en) * | 2016-07-12 | 2021-12-07 | Urgo Recherche Innovation Et Developpement | Dressing enabling the controlled and prolonged release of metformin |
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Application publication date: 20151209 |