CN102949358A - Minodronic acid tablets and preparation method thereof - Google Patents
Minodronic acid tablets and preparation method thereof Download PDFInfo
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- CN102949358A CN102949358A CN2011102366396A CN201110236639A CN102949358A CN 102949358 A CN102949358 A CN 102949358A CN 2011102366396 A CN2011102366396 A CN 2011102366396A CN 201110236639 A CN201110236639 A CN 201110236639A CN 102949358 A CN102949358 A CN 102949358A
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- minodronic acid
- cyclodextrin
- disintegrating agent
- filler
- hydroxypropylβ
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Abstract
The invention belongs to the field of pharmaceutical preparation, and specifically relates to minodronic acid tablets and a preparation method thereof. With large amounts of experiments, proportions of auxiliary materials and hydroxypropyl beta-cyclodextrin are determined, and tablets containing minodronic acid and hydroxypropyl beta-cyclodextrin are prepared. The tablets are composed of minodronic acid, hydroxypropyl beta-cyclodextrin, a filling material, a disintegrating agent, a lubricant, and other pharmaceutically acceptable auxiliary materials. During a preparation process, hydroxypropyl beta-cyclodextrin and minodronic acid are added in a water solution form into mixed powder of the filling material and the disintegrating agent. The dissolution rate of the tablets provided by the invention is substantially improved, such that rapid dissolution and absorption of minodronic acid in gastrointestinal-tract bodily fluids is facilitated. The preparation process is simple, and operation is convenient, such that the method is suitable for industrialized productions.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of minodronic acid tablet and preparation method thereof.
Background technology
Osteoporosis is one group of osteopathia that many reasons causes, the whole world has 200,000,000 people to suffer from osteoporosis approximately at present, and its sickness rate has leapt to commonly encountered diseases, frequently-occurring disease the 7th, and China patient has 90,000,000 approximately.
Minodronic acid is the nitrogenous fragrant heterocycle Diphosphonate of the third generation, by suppressing farnesyl pyrophosphate synthase activity in the osteoclast, the bone resorption that suppresses osteoclast, reduce the bone conversion, play the osteoporotic effect of control, this product is obtained the Japanese health ministry approval on January 21st, 2009 and is gone on the market in Japan by Japanese ONO Pharmaceutical Co., Ltd. and Japanese Astellas Pharmaceutical Co., Ltd joint development.
Minodronic acid is almost insoluble in water, hydrochloric acid solution and phosphate buffer salt (pH6.8), so its In Vitro Dissolution of common process is comparatively difficult.
Patent W09400462A1 discloses the prescription of minodronic acid preparation, and this prescription adding lactose, corn starch, 10% hyprolose aqueous solution, magnesium stearate are made tablet, but its In Vitro Dissolution effect is undesirable;
Patent CN102114025A discloses a kind of technology, and with minodronic acid raw material micronization, with the dissolution of raising minodronic acid, but behind the raw material micronization, easier gathering has increased the difficulty of mixing, and causes easily content inhomogeneous;
Patent CN102078323A discloses a kind of technology, add the additives such as sodium carbonate improving drug dissolution in the minodronic acid preparation, but sodium carbonate alkalescence is stronger, and gastric acid is had destruction, patient's poor compliance.
Summary of the invention
The object of the invention is to overcome the prior art defective, improve the dissolution in vitro of minodronic acid, for this reason, the inventor has carried out a large amount of experiments, determine the ratio of adjuvant and hydroxypropylβ-cyclodextrin, prepared a kind of tablet that contains minodronic acid and hydroxypropylβ-cyclodextrin.
This tablet is comprised of minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent, lubricant and other pharmaceutically acceptable adjuvants.
In the preparation process of the present invention, select the weight ratio of minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent, lubricant to be:
The weight ratio of further preferred minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent, lubricant is:
The weight ratio of most preferred minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent, lubricant is:
Wherein, filler is one or more in lactose, microcrystalline Cellulose, the mannitol, preferably mannitol; Disintegrating agent is one or more in carboxymethyl starch sodium, starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, the low-substituted hydroxypropyl cellulose, preferably polyvinylpolypyrrolidone; Lubricant is one or more in magnesium stearate, silicon dioxide, the Pulvis Talci.
In the preparation process, hydroxypropylβ-cyclodextrin and minodronic acid are to join in the mixed powder of filler and disintegrating agent with the aqueous solution form.
Concrete preparation method may further comprise the steps:
(1) recipe quantity took by weighing filler, the disintegrating agent of 100 mesh sieves, and mix homogeneously is for subsequent use;
(2) in the water-soluble solution of recipe quantity hydroxypropylβ-cyclodextrin, add the minodronic acid of recipe quantity, stir and make dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds lubricant, tabletting, and get final product.
The present invention has obtained good technique effect:
(1) a kind of minodronic acid tablet of the present invention has improved the water solublity of minodronic acid, is conducive to the Fast Stripping of minodronic acid in gastrointestinal tract body fluid.
(2) a kind of minodronic acid tablet of the present invention, fairly simple, easy to operate, the suitable industrialized great production of its preparation process.
The specific embodiment
Now further describe the present invention by following examples, embodiment only is used for the purpose of illustration, does not limit the scope of the invention, and apparent change and modification that while those of ordinary skills make according to the present invention are also contained within the scope of the invention.
The preparation of embodiment 1 minodronic acid tablet
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing mannitol, the polyvinylpolypyrrolidone of 100 mesh sieves, and mix homogeneously is for subsequent use;
(2) in the water-soluble solution of recipe quantity hydroxypropylβ-cyclodextrin, add the minodronic acid of recipe quantity, stir and make dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
The preparation of embodiment 2 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing lactose, the starch of 100 mesh sieves, and mix homogeneously is for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
The preparation of embodiment 3 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing microcrystalline Cellulose, the carboxymethyl starch sodium mix homogeneously of 100 mesh sieves, and was for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds Pulvis Talci, tabletting, and get final product.
The preparation of embodiment 4 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing mannitol, the polyvinylpolypyrrolidone of 100 mesh sieves, and mix homogeneously is for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
The preparation of embodiment 5 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing lactose, the polyvinylpolypyrrolidone of 100 mesh sieves, and mix homogeneously is for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
The preparation of embodiment 6 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing mannitol, the cross-linking sodium carboxymethyl cellulose mix homogeneously of 100 mesh sieves, and was for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds Pulvis Talci, tabletting, and get final product.
The preparation of embodiment 7 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing mannitol, the low-substituted hydroxypropyl cellulose mix homogeneously of 100 mesh sieves, and was for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds silicon dioxide, tabletting, and get final product.
The preparation of comparative example's 1 minodronic acid tablet
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing mannitol, polyvinylpolypyrrolidone, hydroxypropylβ-cyclodextrin, the minodronic acid mix homogeneously of 100 mesh sieves, and was for subsequent use;
(2) add suitable quantity of water in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
The preparation of comparative example's 2 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing mannitol, the polyvinylpolypyrrolidone mix homogeneously of 100 mesh sieves, and was for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
Verify the stripping situation of other prescriptions.
The preparation of comparative example's 3 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
(1) recipe quantity took by weighing microcrystalline Cellulose, pregelatinized Starch, calcium carbonate, the low-substituted hydroxypropyl cellulose mix homogeneously of 100 mesh sieves, and was for subsequent use;
(2) the recipe quantity hydroxypropylβ-cyclodextrin is soluble in water, adds the minodronic acid of recipe quantity, stirs and makes dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds magnesium stearate, tabletting, and get final product.
The preparation of comparative example's 4 minodronic acid tablets
1 minodronic acid tablet prescription
2 preparation technologies
1) preparation of supplementary material and processing were pulverized 100 mesh sieves with minodronic acid, and it is for subsequent use that other adjuvants are crossed respectively 100 mesh sieves;
2) weighing with mix, calculate inventory and take by weighing respectively above-mentioned supplementary material through double checking according to recipe quantity, with above-mentioned supplementary material mix homogeneously;
3) granulate, soft material water processed soft material processed is granulated with 30 order nylon screens, and the granule that makes should lack fine powder, and is neat without rectangular;
4) drying, granulate, total mixed, intermediate check, tabletting, coating and get final product.
Checking embodiment
Dissolution: get this product, according to dissolution method (two appendix XC the second methods of Chinese Pharmacopoeia version in 2010), take water 900ml as dissolution medium, rotating speed is that per minute 50 turns, in accordance with the law operation, when 45min, it is an amount of to get solution, filters, get subsequent filtrate, according to the chromatographic condition under the assay item, precision is measured subsequent filtrate 50 μ l injection liquid chromatographies, the record chromatogram; Precision takes by weighing the about 10mg of minodronic acid reference substance in addition, put in the 100ml measuring bottle, after adding 0.1mol/L sodium hydroxide solution 5ml and making minodronic acid dissolving in ultrasonic 5 minutes, be diluted with water to scale, shake up, precision is measured 1ml and is placed the 100ml measuring bottle, thin up is to scale, shake up, product solution is measured with method in contrast; By the stripping quantity of external standard method with every middle minodronic acid of calculated by peak area, limit is 75% of labelled amount, should be up to specification.
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler, take 0.075% TBAH solution of 10mM tetrasodium pyrophosphate (phosphoric acid is regulated pH7.0)-acetonitrile (95: 5) as mobile phase, the detection wavelength is 218nm, and theoretical cam curve is calculated by the minodronic acid peak should be not less than 3000.
The embodiment dissolution determination the results are shown in Table 1.
Table 1 embodiment dissolution determination result
Annotate: when disintegrate refers to detect dissolution, the disintegrate situation of slice, thin piece.
As seen, embodiment 1-7 disintegrate is rapid from table 1, disintegrate in 5 minutes, and stripping in 10 minutes is complete; The comparative example 1, although disintegrate is rapid, because technological reason, result of extraction is poor; The comparative example 2, although the hydroxypropylβ-cyclodextrin consumption is large, because disintegrate dosage is few, cause the slice, thin piece disintegrate slow, cause dissolution poor; Add cyclodextrin in the prescription of comparative example's 3 employing prior aries, result of extraction is undesirable; Documents 4 adopts prescription and the technique of prior art, and result of extraction is starkly lower than the present invention.This shows that the present invention has obtained unforeseeable technique effect aspect dissolution.
Claims (10)
1. minodronic acid tablet is characterized in that it contains minot phosphoric acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent, lubricant.
2. minodronic acid tablet as claimed in claim 1 is characterized in that the weight ratio of minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent and lubricant is:
3. minodronic acid tablet as claimed in claim 2 is characterized in that the weight ratio of minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent and lubricant is:
4. minodronic acid tablet as claimed in claim 3 is characterized in that the weight ratio of minodronic acid, hydroxypropylβ-cyclodextrin, filler, disintegrating agent and lubricant is:
5. such as each described minodronic acid tablet of claim 1-4, it is characterized in that described filler is one or more in lactose, microcrystalline Cellulose, the mannitol.
6. minodronic acid tablet as claimed in claim 5 is characterized in that described filler is mannitol.
7. such as each described minodronic acid tablet of claim 1-4, it is characterized in that described disintegrating agent is one or more in carboxymethyl starch sodium, starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, the low-substituted hydroxypropyl cellulose.
8. minodronic acid tablet as claimed in claim 7 is characterized in that described disintegrating agent is polyvinylpolypyrrolidone.
9. such as each described minodronic acid tablet of claim 1-4, it is characterized in that described lubricant is one or more in magnesium stearate, silicon dioxide, the Pulvis Talci.
10. method for preparing minot phosphoric acid tablet claimed in claim 1 is characterized in that comprising following steps:
(1) recipe quantity took by weighing filler, the disintegrating agent of 100 mesh sieves, and mix homogeneously is for subsequent use;
(2) in the water-soluble solution of recipe quantity hydroxypropylβ-cyclodextrin, add the minodronic acid of recipe quantity, stir and make dissolving;
(3) (2) solution is all joined in (1), granulate, drying adds lubricant, tabletting, and get final product.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110236639.6A CN102949358B (en) | 2011-08-17 | 2011-08-17 | A kind of minodronic acid tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110236639.6A CN102949358B (en) | 2011-08-17 | 2011-08-17 | A kind of minodronic acid tablet and preparation method thereof |
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| CN102949358A true CN102949358A (en) | 2013-03-06 |
| CN102949358B CN102949358B (en) | 2015-10-21 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106913540A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Minodronic acid tablets and preparation method thereof |
| CN106913546A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Minodronic acid tablets of Fast Stripping and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1443065A (en) * | 2000-07-17 | 2003-09-17 | 山之内制药株式会社 | Pharmaceutical composition improved in peroral absorbability |
| US20060013893A1 (en) * | 2004-07-19 | 2006-01-19 | Stockel Richard F | Bisphosphonates inorganic carriers |
| CN102114025A (en) * | 2011-03-30 | 2011-07-06 | 北京美迪康信医药科技有限公司 | Pharmaceutical composition for treating osteoporosis |
-
2011
- 2011-08-17 CN CN201110236639.6A patent/CN102949358B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1443065A (en) * | 2000-07-17 | 2003-09-17 | 山之内制药株式会社 | Pharmaceutical composition improved in peroral absorbability |
| US20060013893A1 (en) * | 2004-07-19 | 2006-01-19 | Stockel Richard F | Bisphosphonates inorganic carriers |
| CN102114025A (en) * | 2011-03-30 | 2011-07-06 | 北京美迪康信医药科技有限公司 | Pharmaceutical composition for treating osteoporosis |
Non-Patent Citations (1)
| Title |
|---|
| 谢伯泰等: "羟丙基- β - 环糊精特性及其在医药领域中的应用与安全性", 《国外医药--合成药、生化药、制剂分册》, vol. 23, no. 5, 31 December 2002 (2002-12-31) * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106913540A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Minodronic acid tablets and preparation method thereof |
| CN106913546A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Minodronic acid tablets of Fast Stripping and preparation method thereof |
| CN106913546B (en) * | 2015-12-28 | 2021-06-22 | 山东新时代药业有限公司 | Fast-dissolving minodronic acid tablet and preparation method thereof |
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| CN102949358B (en) | 2015-10-21 |
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