挤出-滚圆和流化床包衣法制备硫普罗宁肠溶微丸的研究

目的应用挤出 滚圆法及流化床包衣制备硫普罗宁肠溶微丸，并对其性质进行考察。方法采用国产挤出 滚圆造粒机制备硫普罗宁微丸，采用L9(34)正交设计实验优化工艺条件；用微型流化床包衣设备，将微丸包肠溶衣，考察微丸的粉体学性质及不同包衣增重微丸的体外释放实验。结果制得的硫普罗宁微丸圆整度好，大小均匀。15%包衣增重的微丸体外释放比较理想。结论应用国产挤出 滚圆造粒机制备硫普罗宁微丸，工艺简便，制得的微丸质量好，采用适当的包衣工艺，可制得硫普罗宁肠溶微丸。     

布地奈德肠溶微丸的制备

目的研制布地奈德肠溶微丸。方法采用挤出滚圆工艺及流化床包衣法制备了伐他汀钠肠溶肠溶微丸,并采用正交试验设计对处方进行了优化,考察了微丸的粉体学性质及不同包衣增重微丸的体外释放实验。结果制得的布地奈德微丸圆整度高、收率高、体外释放度好。结论本方法制备工艺简单易行,重现性好,值得进一步的工业化生产。     

挤出-滚圆和流化床包衣法制备盐酸二甲双胍肠溶微丸

目的研制盐酸二甲双胍肠溶微丸。方法采用挤出-滚圆工艺和流化床包衣法制备,用正交试验设计优化处方,考察产品的体外释放度。结果制得的盐酸二甲双胍肠溶微丸圆整度高、收率高、体外释放度好。结论所用制备工艺简单易行,重现性好。     

挤出滚圆-流化床包衣法制备决明子微丸的研究

目的考察并优化挤出滚圆-流化床包衣法制备决明子醇提物微丸的工艺条件。方法采用L9（34）正交设计实验优化制剂工艺条件制备决明子醇提物微丸,考察微丸的粉体学性质,流化制粒包衣机将微丸包衣,并测定体外溶出度。结果以MCC为主要辅料,载药量40%,挤出频率30 Hz,滚圆频率50 Hz,滚圆时间4 min,经流化床包衣制得的决明子醇提物微丸,圆整度、流动性、体外释放度均较理想。结论应用挤出滚圆-流化床包衣法制备决明子醇提物微丸,其工艺简便,成品质量好。     

盐酸文拉法辛缓释胶囊制备

目的研究盐酸文拉法辛缓释胶囊的制备工艺和处方。方法首先用挤出滚圆造粒机制备盐酸文拉法辛微丸,微丸包衣,装胶囊,通过评价微丸的特征、收率和胶囊体外释放度,筛选最佳处方和工艺。结果用挤出滚圆法制备的盐酸文拉法辛微丸圆整度好,收率高。经包衣、填装胶囊制备的盐酸文拉法辛缓释胶囊的释放度与进口盐酸文拉法辛胶囊一致。结论挤出滚圆法制备盐酸文拉法辛微丸工艺简便易行,制得的微丸质量好,收率高;用乙基纤维素包衣获得满意的释放度。     

白术黄连微丸结肠靶向胶囊的制备及体外释放研究

目的将中药“白术黄连方”制备成以胃溶微丸和肠溶微丸为基础的结肠靶向胶囊,优化其处方组成和制备工艺,考察其体外释放特性。方法采用单因素实验和正交实验法优化微丸的处方组成和工艺参数。用挤出-滚圆技术制备素丸,流化床底喷方式进行包衣,考察隔离衣增重、肠溶衣中聚合物比例、增塑剂用量和包衣增重对肠溶微丸释放行为的影响,并对其释药行为进行模型拟合。结果最终确定胃溶微丸的处方为:载药量50%,交联聚维酮(PVPP)5%,微晶纤维(MCC):乳糖=2∶1,润湿剂40%;工艺参数为:挤出速度20 Hz,滚圆速度500 r/min,滚圆时间5 min。肠溶微丸的处方为:载药量27%,PVPP 5%,MCC:乳糖=5∶2,润湿剂30%,粘合剂20%;工艺参数为:挤出速度20 Hz,滚圆速度700 r/min,滚圆时间7 min;肠溶衣处方为:EUDRAGIT?L30D-55:EUDRAGIT?FS30D=1∶2,增塑剂用量10%,包衣增重15%。肠溶微丸的体外释放时间达24 h,其释放行为符合Higuchi模型。结论成功制备了白术黄连微丸结肠靶向胶囊,肠溶微丸表现出缓释和结肠靶向的特性。     

炎琥宁肠溶微丸的制备工艺研究

目的用水分散体系包衣技术制备炎琥宁肠溶微丸给药系统。方法以微晶纤维素(MCC)为填充剂,SiO2为抗黏剂,40%乙醇为黏合剂,采用挤出滚圆法制备丸芯,正交试验设计优化处方和工艺;以Eudragit L 30 D水分散体为包衣材料,乙基纤维素(EC)为阻滞剂,PEG6000为增塑剂,采用流化床包衣法,包肠溶衣层。结果丸芯的最佳处方工艺为:炎琥宁∶MCC∶SiO2=7∶7∶5;挤出速度1 080 r/min,滚圆速度960 r/min,滚圆时间5 min;当EC与Eu-dragit L质量比为35∶65,增塑剂用量为1.71%,聚合物包衣增重为5%时,所制得炎琥宁肠溶微丸在人工胃液(pH1.0)中释放度<10%,在人工肠液(pH 6.8)中正常释放,2 h内释放大于80%,符合中国药典对肠溶制剂释放度的相关规定。结论调整丸芯及包衣的处方工艺参数可以制得体外释放行为符合药典规定的肠溶炎琥宁微丸。     

盐酸多西环素调释微丸的制备及处方因素考察

选用HPMCP-55和HPMC E15作为包衣材料,制备盐酸多西环素调释微丸,并考察其处方因素和工艺.采用流化床底喷溶液上药法制备载药微丸,考察聚合物HPMCP-55和致孔剂HPMC E15之间的比例,聚合物包衣增重以及增塑剂用量和热处理对药物释放的影响.当HPMCP-55和HPMC E15的质量比为25:4,聚合物包衣增重为10%,增塑剂用量为5%时,药物释放行为符合要求.通过调整HPMCP-55和HPMC E15之间的比例,或选择恰当的包衣增重,能使盐酸多西环素载药微丸具备较理想的释放效果.     

盐酸小檗碱结肠控释微丸的制备和体外释放测定

目的制备盐酸小檗碱结肠控释微丸,并初步研究其体外释放行为。方法采用挤出滚圆法制备盐酸小檗碱微丸,旋转包衣锅Eudragit S100包衣,UV法在不同释放条件下测定释放度。结果及结论盐酸小檗碱结肠控释微丸在体外实验中可满足结肠定位释放的要求,使用该方法制备盐酸小檗碱结肠控释微丸有效、可控。     

盐酸沙格雷酯控释微丸的制备及其质量评价

目的:制备盐酸沙格雷酯控释微丸并对其质量进行评价。方法:采用挤出-滚圆工艺制备载药丸芯,以Eurdragit NE30D对丸芯进行流化床包衣,并对影响药物释放的主要因素,如包衣增重,衣膜老化条件等进行考察。结果:所制备的载药丸芯具有较好的圆整度、脆碎度、流动性等;包衣增重7%,50℃老化24 h条件下制得的控释微丸具有较理想的释放行为。结论:制备了适合流化床包衣的盐酸沙格雷酯载药丸芯,以尤特奇水分散体包衣得到了12 h控释微丸。     

盐酸小檗碱结肠定位微丸的制备

目的 制备盐酸小檗碱结肠定位微丸,并初步研究其体外释放行为.方法 采用挤出滚圆法制备盐酸小檗碱微丸,用欧巴代旋转包衣,采用紫外分光光度法测定微丸在不同释放条件下的释放度.结果 制备的盐酸小檗碱微丸在体外试验中可满足结肠定位释放的要求.结论 挤出滚圆法制备盐酸小檗碱结肠定位微丸有效、可控.     

氧化苦参碱微丸的制备及其性质考察

目的:制备氧化苦参碱微丸并考察其性质。方法:用实验型低温挤出滚圆制粒机制备氧化苦参碱微丸;采用L9(34)正交设计优化工艺条件;考察不同含药量的微丸的粉体学性质及体外溶出度。结果:用挤出滚圆法制备的氧化苦参碱微丸圆整度好,大小均匀;最佳工艺为水∶微晶纤维素=0.90∶1,滚圆速度为35Hz,滚圆时间为5min,挤出速度为40Hz;体外溶出度在30min内达到75%以上。结论:挤出滚圆法制备氧化苦参碱微丸的工艺简便易行,制得的微丸质量好。     

Box-Behnken设计-效应面法优化番泻苷微丸的制备工艺

目的:考察挤出-滚圆的工艺参数对番泻苷微丸性质的影响,优化番泻苷微丸的制备工艺。方法:采用挤出-滚圆法制备微丸,以挤出速度、滚圆速度、滚圆时间为自变量,得丸率、圆整度、归一化总值为因变量,采用3因素3水平的Box-Behnken设计进行试验,借助Minitab 14拟合评价指标对自变量的效应面,分析工艺参数对微丸性质的影响,优化微丸制备工艺,并对优化工艺进行验证。结果:最优工艺参数:挤出速度为17 r·min-1,滚圆速度为740 r·min-1,滚圆时间为3 min。该工艺制备的微丸得丸率(84.71±2.38)%,水平面临界角(9.38±0.60)°,总分(0.90±0.04),实测值与预测值(0.86)无显著差异。结论:采用Box-Be-hnken设计-效应面法能够快速得到番泻苷微丸制备工艺的优化模型,实现了工艺的优化。     

挤出滚圆法制备天山雪莲提取物骨架微丸

目的应用挤出滚圆法制备天山雪莲提取物骨架微丸,并研究微丸制备的最佳处方和工艺。方法采用单因素考察和正交设计,用挤出滚圆法筛选天山雪莲提取物骨架微丸最优处方和工艺条件;考察微丸的粉体学性质及累积释放度。结果制得微丸圆整度、均匀度、流动性及堆密度均较好,成品收率高,且30 min内体外释放度均>80%。结论本法制备的雪莲提取物骨架微丸,工艺简便易行,质量可控,收率高。     

Use of chitosan-alginate as alternative pelletization aid to microcrystalline cellulose in extrusion/spheronization

Two types of different molecular weight chitosan were investigated as a pelletization aid in extrusion/spheronization using water as granulation liquid. Spherical pellets with a maximum fraction of 60% w/w chitosan could be produced when 1.25-2.5% w/w sodium alginate was included in the formulations with no microcrystalline cellulose (MCC). Chitosan with lower molecular weight of 190 kDa showed a better pellet forming property. The pellets obtained had acceptable physical characteristics and a fast drug release. The results from Fourier transform infrared spectroscopy, differential scanning calorimetry and (13)C CP-MAS nuclear magnetic resonance spectroscopy confirmed the formation of polyelectrolyte complex (PEC) between chitosan and sodium alginate, which might be a reason for successful pelletization by extrusion/spheronization. Moreover, the presence of PEC might influence the physical characteristics and dissolution behavior of chitosan-alginate pellets. The results indicated an achievement in production of pellets by extrusion/spheronization without using MCC. Moreover, chitosan combined with sodium alginate could be used as a promising alternative pelletization aid to MCC in extrusion/spheronization.     

Properties of drug-containing spherical pellets produced by a hot-melt extrusion and spheronization process

The objectives of this study were to investigate the particle size distribution, morphology and dissolution properties of spherical pellets produced by hot-melt extrusion and spheronization and to compare the properties of hot-melt extruded pellets with beads manufactured by a traditional wet-mass extrusion and spheronization method. Spherical pellets were produced by hot-melt extrusion without the use of water or other solvents. A powder blend of theophylline, Eudragit Preparation 4135 F, microcrystalline cellulose and polyethylene glycol 8000 was hot melt-extruded and the resulting composite rod was cut into cylindrical pellets. The pellets were then spheronized in a traditional spheronizer at an elevated temperature. The same powder blend was processed using conventional wet-mass techniques. Unlike wet-mass extruded pellets, pellets prepared from hot-melt extrusion displayed both a narrow particle size distribution and controlled drug release in dissolution media less than pH 7.4. Scanning electron microscopy, X-ray diffraction and porosity measurements were employed to explain the differences in drug release rates of theophylline from pellets produced by the two processing techniques. Theophylline release from the hot-melt extruded pellets was described using the Higuchi diffusion model, and drug release rates from wet-granulated and melt-extruded pellets did not change after post-processing thermal treatment.     

Enhanced oral bioavailability of novel mucoadhesive pellets containing valsartan prepared by a dry powder-coating technique

The aim of this study was to develop novel mucoadhesive pellets containing valsartan (VAL) with enhanced oral bioavailability. Two types of VAL loaded core pellets were prepared by an extrusion/spheronization method, and further dry-coated with a mixture of hydroxypropylmethylcellulose (HPMC) and carbomer (CB) at different ratios. The effects of the pellet core composition, HPMC:CB ratio and coating level on the drug release from the coated pellets were investigated. The physicochemical properties of the core and coated pellets were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). In addition, the in vitro and in vivo mucoadhesion properties as well as the bioavailability of the coated pellets in rats were evaluated by using VAL suspension and core pellets as control preparations. The results of the release study demonstrated that the two types of core pellets, especially the pellets formulated with a solubilizer and a pH modulator gave considerably faster drug release than the VAL powder. However, the core and coated pellets exhibited similar release profiles indicating that the dry powder-coating did not retard the drug release. Strong molecular interactions were observed between the drug and the carriers in FT-IR analysis. The coated pellets displayed distinct mucoadhesive property in vitro and delayed gastrointestinal (GI) transit in vivo. Furthermore, the coated pellets exhibit significantly higher AUC(0-12h) and C(max), as compared to the core pellets and drug suspension. It was concluded that the mucoadhesive pellets could render poorly water soluble drugs like VAL with a rapid drug release, delayed GI transit and enhanced oral bioavailability.     

Preparation and characterization of a self-emulsifying pellet formulation.

The purpose of the current study is to investigate the feasibility of producing solid self-emulsifying pellets using the extrusion/spheronization technique. Pellets were made from a mixture of C18 partial glycerides, Solutol HS15 and microcrystalline cellulose. Pellets with good physical properties (size, shape, friability) and self-emulsifying properties were produced. The pellets were, in contrast to pellets lacking Solutol, able to transfer a lipophilic dye and a spin probe into the aqueous media. The release kinetics and the microenvironment of the pellets during the release process were assessed using electron spin resonance (ESR) spectroscopy. The ESR results showed that the hydrophobic spin probe was localized mainly in the lipid environment all over the release time. Furthermore, the formulation was capable of accelerating the release of the drug diazepam and achieving a diazepam concentration above its saturation solubility. In conclusion, spherical pellets with low friability and self-emulsifying properties can be produced by the standard extrusion/spheronization technique. The pellets are capable of transfering lipophilic compounds into the aqueous phase and have a high potential to increase the bioavailability of lipophilic drugs.