四乙酰基葛根素双层缓释片的制备及体外释放研究

目的研制四乙酰基葛根素双层片并考察其体外释药特征。方法干法制粒压制双层片,HPLC测定四乙酰基葛根素的释放度。结果考察得到四乙酰基葛根素双层缓释片处方合理,其释药曲线用Higuchi方程拟合,可维持12h持续释放。结论四乙酰基葛根素双层缓释片的研制达到设计要求。     

四乙酰基葛根素自微乳化给药系统的制备及体外评价

目的筛选四乙酰基葛根素自微乳化给药系统的处方并进行体外评价。方法测定四乙酰基葛根素在各种油相、表面活性剂和助表面活性剂中的溶解度,对不同溶剂进行初步配伍研究,采用三元相图法考察不同油相、表面活性剂和助表面活性剂形成微乳的能力,绘制不同处方组成的三元相图,以微乳外观、乳化速度、乳滴粒径、载药量为指标,进一步优选处方,找出最佳的组合和处方配比,制备自微乳化液,测定四乙酰基葛根素自微乳化制剂的溶出度。结果最佳处方体系为Labrafil M1944 cs-Polyoxy 35 castor oil-Transultol P（30∶40∶30）和LauroglycolFCC-Tween 80-Transcutol P（30∶30∶40）,此处方体系能迅速乳化为外观澄清透明的微乳液,粒径分布为（21.6±5.1）、（20.2±9.8）nm,45 min内溶出度分别96.2%、96.7%。结论成功制备了四乙酰基葛根素自微乳化给药系统。     

瑞格列奈二甲双胍缓释片的制备

目的设计并制备瑞格列奈二甲双胍双层片。方法以释放度为指标筛选优化处方。结果以羟丙基纤维素（HPMC）及乙基纤维素（EC）为缓释层辅料,以氯化钠（NaCl）及包衣粉为速释层辅料制备了双层片。缓释层及速释层均可获得良好的溶出行为。结论瑞格列奈二甲双胍双层片的制备工艺简单可行。     

复方缬沙坦双层片的处方筛选及优化

目的:优选由硝苯地平缓释层与缬沙坦速释层组成的双层片处方。方法:先制备硝苯地平固体分散体,以丙烯酸树脂Eudragit NE30D为缓释骨架材料,采用正交试验设计优选处方;然后以缬沙坦在30 min的释放度为评价指标优化速释层的处方。结果:硝苯地平缓释层的最佳处方为Eudragit NE30D(以聚合物干重计)3.0%,乳糖为40%,磷酸氢钙为35%;缬沙坦速释层的最佳处方为乳糖18%、微晶纤维素40%、羧甲基淀粉钠6%、十二烷基硫酸钠10%。结论:正交试验优化的双层片处方良好,达到了设计要求。     

中心复合设计-效应面法优化非洛地平缓释片处方

目的采用中心复合设计 效应面法优化非洛地平缓释片处方。方法以羟丙甲基纤维素（HPMC）K4M和HPMC 100LV的用量为考察因素,以1,4,8 h 的累积释放度（Y1h、Y4h、Y8h）为考察指标,利用二因素三水平中心复合设计 效应面法优化处方,并采用f2相似因子对自制片剂和原研制剂的体外释放度进行比较。结果HPMC K4M和HPMC 100LV的用量各占片剂质量的20.0%和10.0%时,所得缓释片各时间点释放度符合标准;自制片剂和原研制剂在不同释放介质中的释放度相似因子f2分别为70.87,74.19,59.68,69.25。结论HPMC K4M和HPMC 100LV以一定比例联合使用可以有效控制药物释放,采用中心复合设计 效应面法优化的处方预测性良好,制得的非洛地平缓释片体外释放符合要求。     

环维黄杨星D双层片的制备方法及体外评价

目的：研究环维黄杨星D双层片的处方,并进行体外评价（体外释放度）。方法通过单因素考察法分别确定双层片的速释层和缓释层处方组成与制备方法。采用紫外分光光度法测定双层片的体外释放度。结果环维黄杨星D双层片中,速释层处方组成为淀粉、羧甲基淀粉钠、硬脂酸镁,工艺采用湿法制粒;缓释层处方组成为卡波姆、硬脂酸镁,采用干粉末直接压片。体外释放度结果表明,速释层在5 min累积释放度达95%以上,缓释层能在14 h内维持恒定的释药量,满足零级释放方程。结论环维黄杨星D双层片的处方合理,制备工艺简单,可达到速释和缓释的双重作用。     

那格列奈/盐酸二甲双胍双层片的处方优化

目的:优选由那格列奈速释层与盐酸二甲双胍缓释层组成的双层片处方。方法:先以盐酸二甲双胍在2、4、8h时点的释放度与理想值的偏差之和(γ)为评价指标制备缓释层(12h),并采用正交试验设计优选处方;然后在缓释层处方一定的条件下制备双层片,以那格列奈在45min的释放度(Q)为评价指标优化速释层的处方。结果:盐酸二甲双胍缓释层的最佳处方为羟丙基甲基纤维素K4M20%,黏合剂为10%聚维酮K30(PVP)乙醇溶液;那格列奈速释层的最佳处方为乳糖40%,低取代羟丙基纤维素30%,黏合剂为10%PVP乙醇溶液。结论:正交试验优化的双层片处方良好,达到了设计要求。     

星点设计-效应面法优化水飞蓟宾双层片的处方

目的制备难溶性药物水飞蓟宾的双层片,考察其处方因素和体外释药行为,优化水飞蓟宾双层片的处方。方法经单因素考察,确定影响体外释药行为的主要因素,利用星点设计-效应面法优化处方,并对优化处方进行验证。结果缓释层中HPMC K4M、乳糖对水飞蓟宾双层片的体外释药行为有显著影响,依据最优处方制备的缓释片在0.5～12 h内呈良好的缓释释药特征,12 h累积释药率达到80%以上。结论采用星点设计-效应面法得到了水飞蓟宾双层片处方的优化模型,实现了该双层片的处方优化。     

效应面法优化尼美舒利双层缓释片处方

采用正交设计及星点设计-效应面法对尼美舒利双层缓释片处方进行优化。优化后的处方如下：（Ⅰ）速释层：尼美舒利,50 mg;乳糖,92 mg;淀粉,22 mg;CCMC-Na,14 mg;PVP K30,1 mg;微粉硅胶,1 mg;硬脂酸镁,0.9 mg;氧化铁红,0.1 mg;（Ⅱ）缓释层：尼美舒利,150 mg;HPMC K100LV,26 mg;HPMC K4M,33 mg;乳糖,54 mg;PVP K30,1 mg;微粉硅胶,1 mg;硬脂酸镁,0.9 mg。优化后的处方在初期药物快速释放（10 min释放15%）,后期缓慢释放持续一段时间（16 h）,具有双相释放特征,且放置6个月后无明显变化。     

中心复合设计-效应面法优化盐酸米诺环素缓释片处方

摘 要 目的：制备盐酸米诺环素缓释片并优化处方。方法: 采用干法制粒压片工艺制备盐酸米诺环素缓释片,以羟丙甲纤维素E50（HPMC E50）和羟丙甲纤维素K100LV（HPMC K100LV）的用量为考察因素,1,2,4,8 h的累积释放度为评价指标,采用中心复合设计 效应面法优化盐酸米诺环素缓释片的处方,并通过体外释放度比较自研片剂和原研片剂在4种释放介质中的溶出相似性。结果: 盐酸米诺环素缓释片处方中HPMC E50和HPMC K100LV的用量分别为35 mg和70 mg,制得的缓释片在各时间点的释放度与原研片剂相似,4种释放介质中自研片剂和原研片剂的溶出相似因子f₂分别为79.06、84.62、75.46和72.95。结论:采用中心复合设计 效应面法优化的盐酸米诺环素缓释片处方制得的片剂体外释放度符合要求,为下一步的工业化生产提供依据。     

新型抗血吸虫药物QH917自微乳化释药系统的优化和评价

筛选新型抗血吸虫药物QH917自微乳化释药系统的处方。以油相的用量(%)和表面活性剂与助表面活性剂的质量比(K_m)作为自变量，自乳化时间(t)、平均粒径(PS)和多分散系数(PI)作为因变量，采用星点设计——效应面法进行处方优化，模拟体内环境，考察了离子强度、食物、pH值、转速和介质体积对优化处方释放的影响，并采用大鼠在体小肠吸收试验评价了优化处方的吸收情况。结果表明，优化处方为：油相中链甘油三酸酯(MCT)的质量分数为30%～34%，表面活性剂聚氧乙烯40氢化蓖麻油(Cremophor RH40)与助表面活性剂乙醇的质量比为4.8～5.2。优化处方的释放行为基本不受介质环境的影响。大鼠在体小肠吸收试验表明胆管结扎与未结扎对吸收率无显著影响，个体间吸收行为差异性较小。以星点设计——效应面法对自微乳化释药系统的处方进行优化，预测性良好，优化处方体外释放和大鼠小肠吸收行为均比较稳定。     

Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50?R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.     

Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.     

Systematic development of design of experiments (DoE) optimised self-microemulsifying drug delivery system of Zotepine

The aim of present investigation is to improve dissolution rate of poor soluble drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG 400) at apex were used to identify the efficient self-microemulsifying region. Box–Behnken design was implemented to study the influence of independent variables. Principal Component Analysis was used for scrutinising critical variables. The liquid SMEDDS were characterised for macroscopic evaluation, % Transmission, emulsification time and in vitro drug release studies. Optimised formulation OL1 was converted in to S-SMEDDS by using Aerosil^® 200 as an adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC, globule size (152.1?nm), zeta-potential (?28.1?mV), % transmission study (98.75%), in vitro release (86.57%) at 30?min. The optimised solid SMEDDS formulation showed faster drug release properties as compared to conventional tablet of Zotepine.     

丹参酮ⅡA自乳化释药系统制备工艺的研究

 目的：研究丹参酮ⅡA自微乳化释药系统（TanⅡA-SMEDDS）的处方工艺,探求其最佳处方配比。方法：通过溶解度实验、处方配伍实验和三元相图的绘制,以自乳化时间、色泽和粒径大小为指标,筛选油相、表面活性剂、助表面活性剂的最佳搭配和处方配比;并对含药SMEDDS的粒径和载药量进行了测定;绘制了TanⅡA-SMEDDS制剂的溶出曲线。结果：处方选用IPM为油相（35%）,Cremophor RH40/TW80（1∶1）为表面活性剂（40%）,PEG 400为助表面活性剂（25%）。含药微乳的粒径为（61.5±2.7） nm,自乳化时间35 s,载药量为1.948 mg?g-1。体外溶出结果表明10 min内药物的体外溶出可达80%。结论：所制备的TanⅡA-SMEDDS达到了设计要求,为开发TanⅡA新制剂提供了依据。     

环孢菌素A自乳化半固体骨架胶囊的制备

目的考察环孢菌素A自乳化半固体骨架胶囊的处方。方法制备药物的饱和溶液用以测定药物在不同油相中的溶解度;采用伪三元相图法考察不同乳化剂形成微乳的能力和区域,绘制不同处方组成的相图;采用体外乳化实验筛选处方,并制备环孢菌素A自乳化半固体骨架胶囊。结果该胶囊中的乳化剂为Tween 80-聚氧乙烯(40)氢化蓖麻油(质量比为1∶1),助乳化剂为聚乙二醇-8-甘油辛酸/葵酸脂(labrasol),油相为辛酸/癸酸三甘油酯,半固体载体为泊洛沙姆188-硬脂酸聚烃氧(40)酯(质量比为1∶1)。该处方所形成的微乳平均粒径为40 nm。结论按优化处方制得的环孢菌素A自乳化半固体骨架胶囊能够提高环孢菌素A在水中的溶出度。     

Development of novel flurbiprofen-loaded solid self-microemulsifying drug delivery system using gelatin as solid carrier

To develop a novel flurbiprofen-loaded solid self-microemulsifying drug delivery system (solid SMEDDS) with improved oral bioavailability using gelatin as a solid carrier, the solid SMEDDS formulation was prepared by spray-drying the solutions containing liquid SMEDDS and gelatin. The liquid SMEDDS, composed of Labrafil M 1944 CS/Labrasol/Transcutol HP (12.5/80/7.5%) with 2% w/v flurbiprofen, gave a z-average diameter of about 100?nm. The flurbiprofen-loaded solid SMEDDS formulation gave a larger emulsion droplet size compared to liquid SMEDDS. Unlike conventional solid SMEDDS, it produced a kind of microcapsule in which liquid SMEDDS was not absorbed onto the surfaces of carrier but formed together with carrier in it. However, the drug was in an amorphous state in it like conventional solid SMEDDS. It greatly improved the oral bioavailability of flurbiprofen in rats. Thus, gelatin could be used as a carrier in the development of solid SMEDDS with improved oral bioavailability of poorly water-soluble drug.     

双氯芬酸钠自乳化给药系统的研制

目的研制双氯芬酸钠自乳化给药系统。方法通过测定双氯芬酸钠在各种溶剂中的平衡溶解度,选择适宜油相、乳化剂、助乳化剂,并在此基础上绘制伪三元相图。通过对各处方比例的筛选,结合各处方载药量以及所形成微乳的稳定性,确定最佳处方。结果以油相为三辛酸/癸酸甘油酯,乳化剂为Cremophor EL,助乳化剂为丙二醇,Km1为4∶1,Km2为1∶9,双氯芬酸钠在微乳中的质量浓度为25g.L-1,该处方为最佳处方。结论所研制的自乳化给药系统具有粒径小、载药量高、性质稳定的优势,可作为进一步研究的基础。     

注射用葫芦素B自微乳化药物传递系统的处方优化

目的对注射用葫芦素B自微乳化药物传递系统进行处方优化。方法在注射级辅料中筛选油相、乳化剂和助乳化剂,根据空白假三元相图和粒径分析进一步优化处方。结果最佳处方组成为m(油酸乙酯)∶m(Cremophor RH)∶m(乙醇)=30∶55∶15,其中药物含量的质量分数为1%。结论可按照最佳处方组成制备注射用葫芦素B自微乳化药物传递系统。     

胸腺五肽缓释微球的制备及其质量评价

目的确立胸腺五肽（TP-5）微球的制备及质量评价方法。方法以聚乳酸一羟基乙酸（PLGA）为载体材料,采用复乳法（w／o／w）制备TP-5长效缓释注射微球,考察其粒径大小、外观、包封率等理化性质;采用HPLC测定微球中TP-5的含量。结果TP-5微球球形圆整,包封率在80％以上,平均粒径为67．8μm,27d体外累积释放百分率在80％以上．结论TP-5微球的制备工艺合理,评价方法简便、快速、准确。