热熔挤出法制备联苯双酯固体分散体的工艺

目的应用热熔挤出技术制备难溶性药物联苯双酯(bifendate,DDB)的固体分散体,提高DDB的溶出度。方法以共聚维酮(S630)(PVP,N-乙烯基-2-吡咯烷酮和醋酸乙烯酯以质量比为60∶40的比例合成的水溶性共聚物)、PEG6000、丙烯酸树脂Ⅳ为亲水性载体辅料,采用同向双螺杆热熔挤出技术制备DDB固体分散体。比较不同载体挤出物的差示扫描量热图谱和累积溶出曲线,从而判断热熔挤出法对提高DDB溶出度方面的作用。结果采用热熔挤出技术制备的固体分散体可以显著的提高DDB的溶出度。结论采用HME方法制备DDB固体分散体可以显著提高药物的溶出度。     

热熔挤出技术制备螺内酯固体分散体

目的制备螺内酯固体分散体,提高其体外溶出。方法分别以亲水性高分子材料聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物和乙烯吡咯烷酮-醋酸乙烯酯共聚物为载体,采用热熔挤出技术制备螺内酯固体分散体,以有关物质、体外溶出为指标,筛选、优化处方及工艺,并应用差示扫描量热法、X射线衍射法、红外光谱法、偏振光显微镜表征最优固体分散体。结果采用热熔挤出技术可以制备螺内酯固体分散体;最优处方中,螺内酯以分子或无定型状态分散于载体中;固体分散体显著提高了螺内酯在水中的溶出。结论热熔挤出技术制备的固体分散体显著地提高了螺内酯的体外溶出。     

热熔挤出法制备槲皮素固体分散体

目的采用热熔挤出技术制备难溶性药物槲皮素的固体分散体,提高其溶出速率。方法以聚丙烯酸树脂(EudragitEPO)、聚维酮(PVP-K30)、共聚维酮(PVP-VA,Kollidon VA64)为亲水性载体材料,使用双螺杆热熔挤出机制备槲皮素固体分散体,通过体外溶出度测定、差示扫描量热法(DSC)、傅立叶红外光谱(FTIR)和X射线衍射法(XRD)来表征和评价所制备的固体分散体。结果制备的槲皮素固体分散体,与原料药相比,药物溶出得到显著提高,在人工胃液中3 min时处方槲皮素-EPO(1∶9)的药物溶出度可达到67%,处方槲皮素-木糖醇-PVPK30(1∶3∶6)的药物溶出度可达到65%,而在60 min时原料药溶出度不足10%。XRD图谱显示药物晶体衍射峰消失,DSC图谱显示药物熔点吸热峰消失,提示药物是以无定形态分散在载体材料中。结论热熔挤出技术可用于制备槲皮素固体分散体,使药物以无定型态高度分散在载体中,溶出度得到显著提高。     

热熔挤出法制备苯氧乙酸吡嗪酯类化合物FC固体分散体的研究

目的 利用热熔挤出法制备难溶性的药物苯氧乙酸吡嗪酯类化合物FC固体分散体,提高FC的溶出度.方法 选用亲水性的PVPK30、PEG6000、Poloxamer188作为载体辅料,采用热熔挤出技术制备FC固体分散体.通过比较药物FC在不同载体挤出物中的差示扫描量热图和累积溶出曲线图,来判断热熔挤出技术对提高难溶性药物FC溶出度方面的作用.结果 利用热熔挤出法制备的固体分散体能够显著的提高FC的溶出度.结论 用热熔挤出法制备的FC固体分散体,在提高难溶性药物的溶出度方面具有显著的作用.     

热熔挤出技术提高水飞蓟素溶出度的初步研究

目的:研究热熔挤出技术是否提高难溶性药物溶出度.方法:以难溶性水飞蓟素为模型药物,以泊洛沙姆-188为亲水性载体,采用热熔挤出技术和熔融法分别制备挤出物和固体分散体,比较两者的差示扫描量热(DSC)图谱和累积溶出曲线.结果:挤出物是分散程度较高的固体分散体,DSC图谱中药物的吸热峰均消失,载体泊洛沙姆-188的吸热峰向低温方向移动,挤出物中的移行程度大于固体分散体;药物在90 min时从挤出物中溶出90.63%,而在固体分散体中的溶出量为71.06%.结论:热熔挤出技术可提高水飞蓟素的溶出度,且效果优于熔融法.     

阿奇霉素固体分散体制备工艺研究

目的比较不同方法制备难溶性阿奇霉素固体分散体的体外溶出度,优化制备工艺。方法选择不同载体,并采用热熔挤出法和喷雾干燥法制备阿奇霉素固体分散体,并与气流粉碎技术制备的样品比较。采用饱和溶解度和体外累积溶出度判定不同方法所制备成品的差异。结果 2种固体分散体制备技术均能加快药物的溶出度,同时均优于气流粉碎制备的样品。结论相比热熔挤出法,采用喷雾干燥法制备的固体分散体更能显著提高药物的饱和溶解度和溶出度。     

热熔挤出技术制备伊曲康唑固体分散体及体外溶出考察

以羟丙甲纤维素(HPMC E5)为分散载体,利用热熔挤出技术制备难溶性药物伊曲康唑固体分散体,并探究不同挤出工艺参数和增塑剂1,2-丙二醇(PG)含量对固体分散体溶出度的影响。结果表明,二次挤出制得的固体分散体中药物的溶出率大于直接挤出的固体分散体,且二者均明显大于物理混合物。使用PG作增塑剂后伊曲康唑固体分散体的溶出率得到了显著提高,当PG用量较高(10%)时,固体分散体在0.1 mol/L盐酸介质中的溶出率可达到93%。本研究可以为热熔挤出的工艺开发提供更多的思路,同时为进一步制备高规格(200 mg)伊曲康唑片剂提供帮助。     

茴三硫固体分散体的体内外评价

目的采用热熔挤出技术制备茴三硫固体分散体,用于提高其溶出度和口服生物利用度。方法以水溶性聚合物Plasdone S630为载体,用热熔挤出技术制备茴三硫固体分散体。采用差示扫描量热法和X射线粉末衍射法对固体分散体进行表征,并评价其溶出度及犬体内药动学行为。结果药物以无定形或分子状态存在于固体分散体中,溶出速率明显高于参比制剂与物理混合物,在40℃,湿度75%加速6个月,溶出曲线和固体分散体中茴三硫存在状态未发生变化。犬体内药动学研究结果表明,茴三硫固体分散体的Cmax和口服生物利用度是参比制剂的1.66倍和1.57倍。结论采用热熔挤出技术制备的茴三硫固体分散体为热力学稳定体系,能明显提高茴三硫的体外溶出度和口服生物利用度。     

杨梅素固体分散体的制备以及体外溶出试验

目的运用固体分散技术制备杨梅素固体分散体并提高其体外溶出速率。方法选用PEG6000和PVPK30为载体,采用溶剂法和溶剂-熔融法制备杨梅素固体分散体,采用紫外分光光度法进行含量测定,并进行溶解度、体外溶出试验。结果两种载体的固体分散体均能增加药物的溶解度和溶出速率,杨梅素在载体中以高度分散状态存在。结论以PVPK30为载体的杨梅素固体分散体体外溶解度和溶出速率明显提高。杨梅素固体分散体能显著提高杨梅素的溶出速率。     

联苯双酯固体分散体处方及体外性质评价

目的应用不同亲水性载体材料制备联苯双酯固体分散体,提高联苯双酯体外溶出。方法应用溶解度参数法初步筛选载体材料,采用热熔挤出法制备联苯双酯固体分散体,采用差示扫描量热法、X射线粉末衍射法和傅立叶变换红外光谱法对所制备的固体分散体进行表征。对固体分散体进行溶出度测定,以体外累积溶出度为主要指标,分别考察不同载体、不同载药量对固体分散体中联苯双酯溶出度的影响。结果应用不同亲水性载体材料制备的固体分散体均可提高联苯双酯溶出度,其中以Soluplus对联苯双酯溶出度的提高最为显著,累积溶出度可达到90%左右。优选Soluplus为固体分散体载体材料,并且当载药量为20%时,溶出度最高。结论应用载体材料Soluplus制备固体分散体可以显著提高联苯双酯溶出度。载体材料的性质及载药量的高低都会影响固体分散体中药物的溶出度。     

Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder

Preparation of amorphous solid dispersions using hot-melt extrusion process for poorly water soluble compounds which degrade on melting remains a challenge due to exposure to high temperatures. The aim of this study was to develop a physically and chemically stable amorphous solid dispersion of a poorly water-soluble compound, NVS981, which is highly thermal sensitive and degrades upon melting at 165 °C. Hydroxypropyl Methyl Cellulose (HPMC) based polymers; HPMC 3cps, HPMC phthalate (HPMCP) and HPMC acetyl succinate (HPMCAS) were selected as carriers to prepare solid dispersions using hot melt extrusion because of their relatively low glass transition temperatures. The solid dispersions were compared for their ease of manufacturing, physical stability such as recrystallization potential, phase separation, molecular mobility and enhancement of drug dissolution. Two different drug loads of 20 and 50% (w/w) were studied in each polymer system. It was interesting to note that solid dispersions with 50% (w/w) drug load were easier to process in the melt extruder compared to 20% (w/w) drug load in all three carriers, which was attributed to the plasticizing behavior of the drug substance. Upon storage at accelerated stability conditions, no phase separation was observed in HPMC 3cps and HPMCAS solid dispersions at the lower and higher drug load, whereas for HPMCP, phase separation was observed at higher drug load after 3 months. The pharmaceutical performance of these solid dispersions was evaluated by studying drug dissolution in pH 6.8 phosphate buffer. Drug release from solid dispersion prepared from polymers used for enteric coating, i.e. HPMCP and HPMCAS was faster compared with the water soluble polymer HPMC 3cps. In conclusion, of the 3 polymers studied for preparing solid dispersions of thermally sensitive compound using hot melt extrusion, HPMCAS was found to be the most promising as it was easily processible and provided stable solid dispersions with enhanced dissolution.     

Studies on Flash Evaporation for Preparation of Porous Solid Dispersions Using Piroxicam as a Model Drug

An amalgamation of solid dispersion and capillarity has been attempted in present study for enhancement of dissolution rate of poorly soluble drugs. Flash evaporation technique was utilized for enhancement of the dissolution rate of piroxicam. One of the major problems with this drug is its very low solubility in biological fluids, which results in poor bioavailability after oral administration. An attempt was made to enhance the dissolution rate of piroxicam by converting it into porous solid dispersion by flash evaporation method using polyvinylpyrrolidone (PVP) 40,000 as a water-soluble carrier. The resulting solid dispersions were characterized by DSC, FTIR, and X-ray diffraction. In vitro dissolution study revealed significant improvement of dissolution profile of piroxicam. The release of drug from porous solid dispersions containing PVP was superior to those of marketed product, conventional nonporous solid dispersion prepared by solvent evaporation method and drug alone. The steep increase in dissolution rate of porous form is attributable to combined effect of solid dispersion and capillarity.     

热熔挤出法制备阿戈美拉汀固体分散体

目的通过热熔挤出法制备阿戈美拉汀固体分散体。方法以共聚维酮为载体材料,采用热熔挤出技术制备阿戈美拉汀固体分散体。采用X射线粉末衍射技术考察不同比例共聚维酮对固体分散体中药物晶型稳定性的影响。结果当共聚维酮：药物≥2时,样品在高温加速后,其XRPD图谱中无药物晶型衍射峰出现。结论采用热熔挤出技术可以制备出晶型稳定的阿戈美拉汀固体分散体。     

Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion--Part I

Solid dispersions containing different ratios of itraconazole and hydroxypropylmethylcellulose (HPMC) were prepared by solvent casting. Based on dose, differential scanning calorimetry and dissolution results, a drug/polymer ratio of 40/60 w/w was selected in order to prepare dispersions by melt extrusion. The melt extrusion process was characterized using a design of experiments (DOE) approach. All parameter settings resulted in the formation of an amorphous solid dispersion whereby HPMC 2910 5 mPas prevents re-crystallization of the drug during cooling. Dissolution measurements demonstrated that a significantly increased dissolution rate was obtained with the amorphous solid dispersion compared to the physical mixture. The outcome of DOE further indicated that melt extrusion is very robust with regard to the itraconazole/HPMC melt extrudate characteristics. Stability studies demonstrated that the itraconazole/HPMC 40/60 w/w milled melt extrudate formulation is chemically and physically stable for periods in excess of 6 months as indicated by the absence of degradation products or re-crystallization of the drug.     

大黄素固体分散体制备、表征与释药机制研究

摘要：目的 制备大黄素固体分散体，提高其体外溶出度并探究其释药机制。方法 采用分子对接技术，辅助筛选聚合物载体。以大黄素为原料药，Kollidon VA64为聚合物载体，采用热熔挤出工艺制备大黄素固体分散体。通过溶出仪测定其体外溶出，利用SEM，DCS和PXRD对原料药和固体分散体的表面形态和晶型进行表征，最后采用FTIR，NMR和分子动力学模拟对固体分散体的释药机制进行探究。结果 相较于大黄素原料药，大黄素固体分散体在4种介质中的溶出被明显改善，大黄素由结晶态转化为无定形态，药物与聚合物载体间形成了氢键。结论 固体分散体中药物晶型的转变和氢键的产生是改善药物体外溶出的主要因素。