CN103054822B - Imidafenacin tablet and preparation method thereof - Google Patents
Imidafenacin tablet and preparation method thereof Download PDFInfo
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- CN103054822B CN103054822B CN201210585889.5A CN201210585889A CN103054822B CN 103054822 B CN103054822 B CN 103054822B CN 201210585889 A CN201210585889 A CN 201210585889A CN 103054822 B CN103054822 B CN 103054822B
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Abstract
The invention discloses an imidafenacin tablet which is prepared from the components including imidafenacin, water-soluble polymer, a filling agent, a disintegrating agent and lubricant; the water-soluble polymer is selected from one or more of poloxamer, polyethyleneglycol, hydroxypropyl methylcellulose, polyvinyl alcohol and copovidone and accounts for 0.1 percent to 3 percent (w/w) of the total weight of the whole tablet; and the disintegrating agent is pregelatinized starch or a mixture of common starch and pregelatinized starch and accounts for 15 percent to 50 percent (w/w) of the total weight of the whole tablet. The tablet provided by the invention can be dissolved in a water-based medium at an unexpected high level in relative time and has a very good dissolution characteristic and remarkable physical stability.
Description
Technical field
The invention belongs to pharmaceutical preparations technology field, in particular to a kind of imidafenacin tablet and preparation method thereof, relate in particular to a kind of imidafenacin tablet and technique thereof that adopts solid dispersions technique to prepare.
Background technology
Imidafenacin (Imidafenacin) has diphenyl butanamide structure, is a kind of new and effective anticholinergic agent, and its selectively acting is in M3 and M1 receptor, and the contraction of blocking-up choline to detrusor, makes detrusor lax, reduces side effects of pharmaceutical drugs.Imidafenacin has the contraction of the smooth muscle of bladder of inhibition and suppresses the free dual function of acetylcholine simultaneously, and the selectivity of bladder is better than to salivary gland, for in cerebral tissue but alkali receptor affinity is lower, therefore maincenter and periphery untoward reaction are less, there is height bladder selectivity, be applicable to the treatment of overactive bladder.
Imidafenacin chemistry 4-(2-methyl-1 H-imidazole-1-group)-2 by name, 2-diphenyl butanamide, structural formula is as shown in formula I, for white is to off-white color crystalline powder, be soluble in acetic acid (100), be dissolved in N, N-dimethyl adds amide and methanol, slightly be dissolved in ethanol (99.5), be slightly soluble in acetonitrile, be insoluble in water.
Due to active component imidafenacin poorly water-soluble, cause the bioavailability of preparation or absorption in vivo very low, thereby cause the inadequate problem of drug effect.In order to increase its water solublity, and then increase its oral administration biaavailability, those skilled in the art can consider to adopt solid dispersions technique to prepare imidafenacin tablet, and active component imidafenacin is scattered in polymer supported liquid solution with unbodied state.Yet, owing to adopting the imidafenacin tablet of conventional solid dispersion powder preparation significantly to reduce the specific surface area of slice, thin piece itself, and the strong combination in mold process between the plastic deformation of amorphous drug molecule and carrier polymer, therefore adopts the imidafenacin tablet porosity of solid dispersion powder preparation generally very low.This low-porosity makes hydrone in drug administration process slowly infiltrate tablet, so solid dispersion is difficult to performance, and it improves the internal action of stripping.In addition, in hydration or process in leaching, as the viscosity of the water-soluble or enteric polymer of carrier, increase, thereby in process in leaching, on the surface of tablet, form a kind of hydrogel layer, the infiltration of water is further stoped.
CN101983054A discloses rapid disintegrative tablet in a kind of oral cavity of containing imidafenacin, it contains the compositions that (1) contains excipient and disintegrating agent with polyvidone or gastric solubility macromolecule granules coating, that contain imidafenacin or imidafenacin granule, with (2), and the compressed shaping of described compositions.Yet, what this imidafenacin tablet adopted is fluidized-bed spray granulation, the filleies such as imidafenacin and starch are prepared into granule, then water-soluble polymer is sprayed to the outside of parcel and granule, then at tabletting, say the tablet that has obtained having certain light-shading effect, but this kind of way obtains granule after tabletting, the water-solubility membrane clothing of parcel can break under the effect of pressure in deformation, and the preparation tablet weight of this patent is bigger than normal, complex manufacturing is infeasible, has increased a lot of production costs, and efficiency is lower.
CN102579393A discloses a kind of solid composite medicament containing imidafenacin, with hydrophilicity condiment and imidafenacin micronization, the material particular diameter that requirement obtains is less than 5 microns, yet the operational approach of this patent is in commercial production efficiency, lower and micronizing materials particle diameter reproducibility needs to be investigated.
Summary of the invention
In view of the deficiencies in the prior art, the present invention studies the solid dispersion technology of preparing of imidafenacin by lot of experiments, find when adding the water-soluble polymer of particular types and consumption and disintegrating agent, the disintegrative of the tablet obtaining by mold pressing solid dispersion does not reduce, and has excellent dissolution.Therefore, the object of the present invention is to provide a kind of equal stable and imidafenacin tablet that can Fast Stripping under various conditions, and the method for preparing said preparation.
The object of the present invention is achieved like this:
A kind of imidafenacin tablet, by the component that comprises imidafenacin, water-soluble polymer, filler, disintegrating agent and lubricant, be prepared from, described water-soluble polymer be selected from polyethylene adjoin pyrrolidone, hypromellose, Polyethylene Glycol, polyvinyl alcohol and poloxamer one or more, consumption accounts for the 0.1-3%(w/w of whole weight), described disintegrating agent is the mixture of pre-paying starch or common starch and pregelatinized Starch, and that consumption accounts for whole weight is 15-50%(w/w).
Preferably, above-mentioned imidafenacin tablet, wherein said water-soluble polymer is poloxamer, preferably consumption accounts for the 0.5-2%(w/w of whole weight).
Preferably, above-mentioned imidafenacin tablet, wherein said disintegrating agent is pre-paying starch, that consumption accounts for whole weight is 23.5-33.5%(w/w).
Preferably, the imidafenacin tablet of the above, wherein said filler is selected from one or more of microcrystalline Cellulose, starch, lactose, sucrose, mannitol and anhydrous calcium phosphate.
Further preferably, above-mentioned imidafenacin tablet, wherein said filler is microcrystalline Cellulose.
Preferably, above-mentioned imidafenacin tablet, wherein said lubricant is selected from one or more of magnesium stearate, Pulvis Talci, castor oil hydrogenated, stearic acid and Polyethylene Glycol.
A preparation method for above-mentioned imidafenacin tablet, comprises the steps: water-soluble polymer dissolves in solvent, adds imidafenacin make dispersed or dissolve, mix with filler and disintegrating agent, wet granulation, 40 ℃-60 ℃ dry, direct compression after dry granule and mix lubricant.
The preparation method of above-mentioned imidafenacin tablet, wherein said solvent is preferably the aqueous solution of methanol, ethanol, dichloromethane or acetone.
Compared with prior art, the imidafenacin tablet the present invention relates to and preparation method thereof tool has the following advantages and is significant progressive: the whole disintegrates of medicine in the tablet of the imidafenacin that the present invention obtains 10 minutes, it is more than 85% that the concentration of imidafenacin in stripping system is dosage, therefore shows high disintegrative and high stripping property.
Accompanying drawing explanation
Fig. 1 is the stripping curve figure of the imidafenacin sheet of embodiment 1 and comparative example 1 preparation.
Fig. 2 is the stripping curve figure of the imidafenacin sheet of embodiment 2 and comparative example 2 preparations.
Fig. 3 is the stripping curve figure of the imidafenacin sheet of embodiment 3 and comparative example 3 preparations.
The specific embodiment
Form is described in further detail foregoing of the present invention again by the following examples, but this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following embodiment, all technology realizing based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1 and comparative example 1:
| Prescription | Embodiment 1 | Comparative example 1 | |
| Imidafenacin | 0.1g | 0.1g | |
| Microcrystalline Cellulose (PH101) | 100g | 100g | |
| Pregelatinized Starch | 32g | 32g | |
| Magnesium | 1g | 1g | |
| 70% alcohol solvent | In right amount | ||
| 5% poloxamer ethanol (70%) solution | 1.5g(is in poloxamer) |
Embodiment 1 preparation technology: poloxamer is dissolved in 70% ethanol water, add imidafenacin make dispersed or dissolve, the microcrystalline Cellulose (PH101) and the pregelatinized Starch that then add the recipe quantity of mix homogeneously, wet granulation, 40 ℃-60 ℃ dry, after dry granule mixes with magnesium stearate, directly presses 1000.
Comparative example 1 preparation technology: imidafenacin is mixed homogeneously with microcrystalline Cellulose (PH101) and pregelatinized Starch, using 70% ethanol water as binding agent, wet granulation, 40 ℃-60 ℃ are dry, after dry granule mixes with magnesium stearate, directly press 1000.
Stripping curve figure (accompanying drawing 1) by the imidafenacin sheet of embodiment 1 and comparative example 1 preparation can find out, the stripping of imidafenacin tablet prepared by water-soluble polymer has obvious quickening.
Embodiment 2 and comparative example 2:
| Prescription | Embodiment 2 | Comparative example 2 |
| Imidafenacin | 0.1g | 0.1g |
| Microcrystalline Cellulose (PH101) | 100g | 100g |
| Pregelatinized Starch | 32g | 32g |
| Magnesium stearate | 1g | 1g |
| 5%PVP.K30 ethanol (70%) solution | 1.5g(is in PVP.K30) | |
| 5% poloxamer ethanol (70%) solution | 1.5g(is in poloxamer) |
Embodiment 2 preparation technologies: poloxamer is dissolved in 70% ethanol water, add imidafenacin make dispersed or dissolve, then add the microcrystalline Cellulose of the recipe quantity of mix homogeneously (PH101) and pregelatinized Starch, wet granulation, 40 ℃-60 ℃ dry, after dry granule mixes with magnesium stearate, directly presses 1000.
Comparative example 2 preparation technologies: imidafenacin is mixed with microcrystalline Cellulose (PH101) and pregelatinized Starch, using 5%PVP.K30 ethanol (70%) solution as binding agent, wet granulation, 40 ℃-60 ℃ dry, after dry granule mixes with magnesium stearate, directly presses 1000.
The stripping curve figure (accompanying drawing 3) of the imidafenacin sheet of being prepared by embodiment 2 and comparative example 2 can find out, adopts the stripping of the imidafenacin tablet of preparation technology's acquisition of the present invention to have obvious quickening.
Embodiment 3 and comparative example 3:
Preparation process: poloxamer is dissolved in 70% ethanol water, add imidafenacin make dispersed or dissolve, then add the microcrystalline Cellulose of the recipe quantity of mix homogeneously (PH101) and pregelatinized Starch, wet granulation, 40 ℃-60 ℃ dry, after dry granule mixes with magnesium stearate, directly presses 1000.
Stripping curve figure (accompanying drawing 3) by the imidafenacin sheet of embodiment 3 and comparative example 3 preparations can find out, adopts the dissolution of imidafenacin tablet prepared by the poloxamer of large recipe quantity can reduce on the contrary, also increases production cost simultaneously.
Claims (7)
1. an imidafenacin tablet, it is characterized in that: by the component that comprises imidafenacin, water-soluble polymer, filler, disintegrating agent and lubricant, be prepared from, described water-soluble polymer is poloxamer, consumption accounts for the 0.5-2%(w/w of whole weight), described disintegrating agent is the mixture of pregelatinized Starch or common starch and pregelatinized Starch, and consumption accounts for the 15-50%(w/w of whole weight).
2. imidafenacin tablet according to claim 1, is characterized in that: described disintegrating agent is pregelatinized Starch, and consumption accounts for the 23.5-33.5%(w/w of whole weight).
3. imidafenacin tablet according to claim 1, is characterized in that: described filler is selected from one or more of microcrystalline Cellulose, starch, lactose, sucrose, mannitol and anhydrous calcium phosphate.
4. imidafenacin tablet according to claim 1, is characterized in that: described filler is microcrystalline Cellulose.
5. imidafenacin tablet according to claim 1, is characterized in that: described lubricant is selected from one or more of magnesium stearate, Pulvis Talci, castor oil hydrogenated, stearic acid and Polyethylene Glycol.
6. the preparation method of imidafenacin tablet according to claim 1, it is characterized in that: comprise the steps: water-soluble polymer dissolves in solvent, add imidafenacin make dispersed or dissolve, mix with filler and disintegrating agent, wet granulation, 40 ℃-60 ℃ dry, direct compression after dry granule and mix lubricant.
7. the preparation method of imidafenacin tablet according to claim 6, is characterized in that: described solvent is the aqueous solution of methanol, ethanol, dichloromethane or acetone.
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| CN201210585889.5A CN103054822B (en) | 2012-12-28 | 2012-12-28 | Imidafenacin tablet and preparation method thereof |
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| CN201210585889.5A CN103054822B (en) | 2012-12-28 | 2012-12-28 | Imidafenacin tablet and preparation method thereof |
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| CN103054822B true CN103054822B (en) | 2014-03-26 |
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| CN104415034B (en) * | 2013-08-29 | 2018-03-02 | 天津药物研究院有限公司 | A kind of imidafenacin pharmaceutical composition and preparation method thereof |
| CN103479594B (en) * | 2013-09-29 | 2015-05-20 | 扬子江药业集团四川海蓉药业有限公司 | Imidafenacin film-coated tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579393A (en) * | 2012-03-19 | 2012-07-18 | 北京德众万全药物技术开发有限公司 | Solid composition for improving content uniformity and dissolution rate of imidafenacin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102579393A (en) * | 2012-03-19 | 2012-07-18 | 北京德众万全药物技术开发有限公司 | Solid composition for improving content uniformity and dissolution rate of imidafenacin |
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