CN102657617A - Hot-melt extruded quick release preparation of nimesulide and hot-melt extruding method thereof - Google Patents
Hot-melt extruded quick release preparation of nimesulide and hot-melt extruding method thereof Download PDFInfo
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- CN102657617A CN102657617A CN2012101426248A CN201210142624A CN102657617A CN 102657617 A CN102657617 A CN 102657617A CN 2012101426248 A CN2012101426248 A CN 2012101426248A CN 201210142624 A CN201210142624 A CN 201210142624A CN 102657617 A CN102657617 A CN 102657617A
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Abstract
The invention belongs to the field of pharmacy and relates to a hot-melt extruded quick release preparation of nimesulide and a hot-melt extruding method thereof. The hot-melt extruded quick release preparation is mainly characterized in that copovidone (PVP-VA64, Kollidon VA64) or povidone (PVPK30) serves as a main dispersing carrier material, and when necessary, a sugar alcohol auxiliary material serving as a plasticizer is added into the main dispersing carrier material, so that the aims of reducing extruding temperature and simplifying an extruding process are fulfilled. And due to the adoption of a nimesulide solid dispersion, the hot-melt extruded quick release preparation has the characteristic of quick dissolution.
Description
Technical field
The invention belongs to pharmaceutical field, relate to a kind of hot melt extrusion method, be used to prepare the quick releasing formulation of nimesulide.
Background technology
Nimesulide is a kind of NSAID, and the alternative Cycloxygenase II that suppresses has significant antiinflammatory, analgesia and refrigeration function; But nimesulide is a kind of slightly water-soluble crystalline pharmaceutical; Dissolubility is little, and bioavailability is low, and there is gastrointestinal side effect in oral administration.The method that improves the insoluble drug bioavailability commonly used has micronization technology and solid dispersion technology.After the drug micronization, surface free energy is bigger, and the trend of spontaneous coalescence is arranged, and has reduced the micronization effect.Utilize the highly-water-soluble carrier material to be prepared into solid dispersion insoluble drug at present, improve drug solubility, to accelerate the medicine dissolution rate remarkably productive, obtains increasingly extensive concern and application.Traditional solid dispersion preparation has: fusion method, solvent method, polishing, spray drying method, but because these method for preparinies exist problems such as complex process, repeatability are low, organic solvent residual, the industrialization promotion difficulty is bigger.The hot melt extrusion molding is a new preparation solid dispersions technique that is applied to field of pharmaceutical preparations in recent years; It is added to crude drug, polymer adjuvant in the extruder simultaneously; Make material experience Solid Conveying and Melting, fusion, three stages of melt Conveying; Under the powerful shear action of kneading device and screw element, obtain the dispersive shaped article of high mixed, particularly valuable is that preparation technology is easy to realize industrial amplification production.
The patent application that early stage, Ceng Youyong hot melt extruding technology prepared the indomethacin solid dispersion (adopts polynary adjuvant to prepare the hot melt expressing technique of indomethacin quick releasing formulation; Application number: 201110122431.1); But only relate to a kind of medicine, and used adjuvant contains gelatin more.
The present invention is directed to the medicine nimesulide and carry out the preparation that hot melt is extruded solid dispersion; Polyvidone (PVPK30) or copolyvidone (PVP-VA64 have mainly been adopted; Kollidon VA64) as the dispersible carrier material, add the sugar alcohols adjuvant in case of necessity as plasticizer, can reduce temperature facilitation expressing technique process; Can obtain the screw rod shearing effect of sufficient intensity again, thereby effectively improve the dispersity of medicine in carrier.
In addition, the stripping of nimesulide has stronger pH value dependency to medium, and with the rising of dissolution medium pH value, its dissolution rate is accelerated, and dissolution increases.In nearly neutral pH 7.4 or lower pH dissolution medium, the dissolution of medicine itself is lower.The present invention is directed to nimesulide medicine own characteristic, adopt the hot melt extruding technology to prepare quick-releasing type nimesulide solid dispersion, make the dissolution in vitro of medicine in the pH7.4 aqueous medium obtain raising by a relatively large margin.
Summary of the invention
The hot melt that the invention provides a kind of quick-releasing type nimesulide solid dispersion is extruded method for preparing; Principal character is with hydrophilic high molecular material copolyvidone (PVP-VA64; Kollidon VA64) or polyvidone (PVPK30) as main dispersible carrier material, add the sugar alcohols adjuvant in case of necessity as plasticizer, facilitation expressing technique process; Effectively improve the dispersity of medicine in solid dispersion, improve the dissolution of nimesulide.
The present invention realizes through following measure:
A kind of hot melt of nimesulide solid dispersion is extruded quick releasing formulation, it is characterized in that comprising following component in percentage by weight:
Nimesulide 5～20%
Hydrophilic high molecular material 70～90%
Plasticizer 0～20%
Described hydrophilic high molecular material is copolyvidone (PVP-VA) or polyvidone (PVP).
Described plasticizer is one or more in sorbitol, xylitol, mannitol, Polyethylene Glycol, the poloxamer.
The hot melt of described nimesulide solid dispersion is extruded the hot melt expressing technique of preparation, it is characterized in that may further comprise the steps:
1) respectively crude drug nimesulide and pharmaceutic adjuvant pulverizing back are crossed 60～100 mesh sieves, mix in proportion, process physical mixture; Pharmaceutic adjuvant is above-mentioned hydrophilic high molecular material and plasticizer;
2) extrusion temperature of setting double screw extruder is 110～150 ℃, and temperature starts screw rod after being raised to setting value, and the physical mixture in the step 1) is added in the extruder, through fusion, extruding, extrudes with ribbon at last;
3) after the cooling of ribbon extrudate, pulverization process is crossed the 20-80 mesh sieve, obtains medicine solid dispersion granule or powder.
Said hot melt expressing technique is characterized in that further comprising the steps of:
4) step 3) gained granule or powder be as granule or powder direct packaging, perhaps is processed into capsule, tablet, lamination method and is wrapped on the micropill or at the preparation outer surface and wraps enteric coating, processes corresponding solid preparation.
The present invention has following beneficial effect:
1, the nimesulide solid dispersion of the present invention's preparation all can reach the effect of quick stripping in the aqueous medium of pH >=7.4.
2, the preparation technology among the present invention is simple, and energy consumption is little, no solvent residue, and whole process can not introduced other impurity, is easy to realize continuous mass production.Through fusion, screw rod shearing and extruding, medicine disperses more even in carrier material.
Description of drawings
Differential scanning calorimetric analysis (DSC) collection of illustrative plates of the nimesulide solid dispersion of preparation, physical mixture, nimesulide crude drug among Fig. 1, the embodiment 1;
Differential scanning calorimetric analysis: the sample that takes by weighing 5 milligrams places the aluminum dish, is reference substance with the aluminium oxide, and the intensification scope is 25 ℃～200 ℃ in nitrogen current, with 10 ℃/min
-1The speed scanning that heats up.
The powder x-ray diffraction collection of illustrative plates of the nimesulide solid dispersion of preparation, physical mixture, nimesulide crude drug among Fig. 2, the embodiment 1;
Powder x-ray diffraction is analyzed: the copper target, and pipe is pressed 40KV, pipe flow 200mA, scanning angle 2 θ angles are 5-45 °, scanning speed is 5 °/min.
The medicine stripping curve figure of the nimesulide solid dispersion of preparation, physical mixture, nimesulide crude drug among Fig. 3, the embodiment 1.
Dissolution determination: the accurate weighting raw materials of difference, physical mixture, extrudate powder an amount of (being equivalent to the about 50mg of medicine), according to 2010 editions two appendix XC second methods of Chinese Pharmacopoeia, 900mL is a dissolution medium with phosphate buffer (pH7.4), rotating speed is 60r/mi n; In 2,5,10,15; 20,30,45, get solution 6ml during 60min; And replenishing uniform temp simultaneously, the dissolution medium of equal volume through the microporous filter membrane filtration of 0.45 μ m, is got the subsequent filtrate dilution; Measure absorbance in the 393nm wavelength, according to standard curve equation (C=22.854A-0.0713, r
2=0.9996) calculates medicine accumulative total stripping quantity.
The specific embodiment
Below in conjunction with the accompanying drawing and the specific embodiment the present invention is described further.Should be understood that following explanation only is in order to explain the present invention, its content not to be limited.If no special instructions, the content of following used each composition content that is weight percentage.
Embodiment 1
Nimesulide (10%), xylitol (10%), PVPK30 (80%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 145 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 77%, 5min reaches 84%; The stripping of its physical mixture is respectively 16%, 29%; Crude drug stripping when 45min is 22%.
Embodiment 2
Nimesulide (20%), xylitol (5%), PVPK30 (75%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 145 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 74%, 10min reaches 85%.
Embodiment 3
Nimesulide (10%), PVP-VA64 (90%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 145 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 67%, 5min reaches 82%.
Embodiment 4
Nimesulide (10%), xylitol (5%), PVP-VA64 (80%), glyceryl monostearate (5%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 125 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 70%, 5min reaches 82%.
Embodiment 5
Nimesulide (10%), xylitol (5%), PVP-VA64 (85%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 135 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 69%, 5min reaches 82%.
Embodiment 6
Nimesulide (5%), sorbitol (5%), PVP-VA64 (90%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 140 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 78%, 5min reaches 90%.
Embodiment 7
Nimesulide (10%), sorbitol (5%), PVP-VA64 (85%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 140 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 60 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 5min stripping 70%, 15min reaches 85%.
Embodiment 8
Nimesulide (10%), xylitol (20%), PVPK 30 (70%) mix homogeneously are prepared into physical mixture; Extruder temperature is set at 145 ℃, treat temperature be raised to setting value and stable after, at the uniform velocity add physical mixture; Obtain the ribbon extrudate; 40 mesh sieves were pulverized in cooling, obtained nimesulide solid dispersion granule.External dissolution test result, 2min stripping 75%, 5min reaches 81%.
Claims (4)
1. the hot melt of a nimesulide solid dispersion is extruded quick releasing formulation, it is characterized in that comprising following component in percentage by weight:
Nimesulide 5～20%
Hydrophilic high molecular material 70～90%
Plasticizer 0～20%
Described hydrophilic high molecular material is copolyvidone or polyvidone.
2. the hot melt of nimesulide solid dispersion according to claim 1 is extruded preparation, it is characterized in that: described plasticizer is one or more in sorbitol, xylitol, mannitol, Polyethylene Glycol, poloxamer, the glyceryl monostearate.
3. the hot melt of nimesulide solid dispersion according to claim 1 is extruded the hot melt expressing technique of preparation, it is characterized in that may further comprise the steps:
1) respectively crude drug nimesulide and pharmaceutic adjuvant pulverizing back are crossed 60～100 mesh sieves, mix homogeneously is processed physical mixture; Pharmaceutic adjuvant is above-mentioned hydrophilic high molecular material and plasticizer;
2) extrusion temperature of setting double screw extruder is 110～150 ℃, and temperature starts screw rod after being raised to setting value, and the physical mixture in the step 1) is added in the extruder, through fusion, extruding, extrudes with ribbon at last;
3) after the cooling of ribbon extrudate, pulverization process is crossed the 20-80 mesh sieve, obtains medicine solid dispersion granule or powder.
4. according to the said hot melt expressing technique of claim 3, it is characterized in that further comprising the steps of:
4) step 3) gained granule or powder be as granule or powder direct packaging, perhaps is processed into capsule, tablet, lamination method and is wrapped on the micropill or at the preparation outer surface and wraps enteric coating, processes corresponding solid preparation.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210142624.8A CN102657617B (en) | 2012-05-09 | 2012-05-09 | Hot-melt extruded quick release preparation of nimesulide and hot-melt extruding method thereof |
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| CN201210142624.8A CN102657617B (en) | 2012-05-09 | 2012-05-09 | Hot-melt extruded quick release preparation of nimesulide and hot-melt extruding method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006568A (en) * | 2013-01-05 | 2013-04-03 | 中国科学院苏州纳米技术与纳米仿生研究所 | Felodipine solid dispersion (SD) and preparation method thereof |
| CN104523644A (en) * | 2015-01-27 | 2015-04-22 | 严白双 | Rapidly-dissolved loratadine tablets and preparation process thereof |
| CN108338974A (en) * | 2017-01-24 | 2018-07-31 | 复旦大学 | BF061 solid dispersions and preparation method thereof and the purposes in pharmacy |
| CN110859807A (en) * | 2018-08-28 | 2020-03-06 | 康芝药业股份有限公司 | Nimesulide solid dispersion micro powder and preparation method thereof |
| CN111632031A (en) * | 2019-02-22 | 2020-09-08 | 康芝药业股份有限公司 | Application of nimesulide solid dispersion micro powder |
-
2012
- 2012-05-09 CN CN201210142624.8A patent/CN102657617B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 赵优曼等: "热熔挤出法制备尼美舒利固体分散体", 《2011年中国药学大会暨第11届中国药师周论文集》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006568A (en) * | 2013-01-05 | 2013-04-03 | 中国科学院苏州纳米技术与纳米仿生研究所 | Felodipine solid dispersion (SD) and preparation method thereof |
| CN104523644A (en) * | 2015-01-27 | 2015-04-22 | 严白双 | Rapidly-dissolved loratadine tablets and preparation process thereof |
| CN104523644B (en) * | 2015-01-27 | 2017-06-20 | 江苏联环药业股份有限公司 | The Loratadine tablet and its preparation technology of a kind of Fast Stripping |
| CN108338974A (en) * | 2017-01-24 | 2018-07-31 | 复旦大学 | BF061 solid dispersions and preparation method thereof and the purposes in pharmacy |
| CN108338974B (en) * | 2017-01-24 | 2020-09-01 | 复旦大学 | BF061 solid dispersion, preparation method and application thereof in pharmacy |
| CN110859807A (en) * | 2018-08-28 | 2020-03-06 | 康芝药业股份有限公司 | Nimesulide solid dispersion micro powder and preparation method thereof |
| CN111632031A (en) * | 2019-02-22 | 2020-09-08 | 康芝药业股份有限公司 | Application of nimesulide solid dispersion micro powder |
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Granted publication date: 20140402 Termination date: 20180509 |