盐酸青藤碱缓释微丸的研制

目的制备盐酸青藤碱缓释微丸,并对其体外释药情况进行研究。方法采用离心造粒技术制备微晶纤维素空白丸核和盐酸青藤碱含药丸芯,以聚丙烯酸树脂Eudragit NE 30D为包衣液制成膜控缓释微丸,考察包衣增重、抗粘剂用量等因素对缓释微丸释放度的影响。结果通过单因素考察确定了包衣液处方,所制备的微丸具有明显的缓释特征,体外释药过程符合一级动力学模型。结论用聚丙烯酸树脂Eudragit NE30D作为包衣材料所得缓释微丸符合24 h缓释要求。     

盐酸青藤碱缓释微丸的研制

目的：制备盐酸青藤碱缓释微丸，并对其体外释药行为进行研究。方法：采用离心造粒技术制备盐酸青藤碱素丸，在流化床内采用丙烯酸树脂水分散体对其包衣，制备盐酸青藤碱缓释微丸。对包衣材料种类、配比及用量进行选择，对包衣微丸体外释药机理进行研究。结果：包衣材料Eudragit NE30D增重5％时，包衣微丸在水中呈现良好的缓释效果，体外释药过程基本符合Higuchi方程：Y=0．0938＋0．0846t（r=0．9965）。结论：采用离心造粒技术和丙烯酸树脂流化床包衣，成功地制备了盐酸青藤碱缓释微丸，其体外释药缓慢、平稳。     

苦参碱结肠靶向微丸的制备及体外释放性能评价

目的:优选苦参碱结肠靶向微丸的制备工艺。方法:采用挤出-滚圆法制备苦参碱载药丸芯,利用流化床包衣技术对苦参碱载药丸芯进行包衣,并进行体外释放度的考察。结果:苦参碱载药丸芯的优化处方工艺为:苦参碱10g,微晶纤维素40g,羧甲基纤维素钠0.5g,纯化水46mL。其包衣微丸外层衣尤特奇L30D-55增重20%,内层衣尤特奇EPO增重30%。体外释放度实验表明,苦参碱包衣微丸在模拟的胃液中基本不释放,在pH 5.0磷酸缓冲液中较快释放,在pH 6.8磷酸缓冲液中则释放缓慢。结论:苦参碱载药丸芯处方工艺简单稳定。苦参碱包衣微丸结肠靶向性较好,同时模拟实验提示在结肠pH发生明显下降时苦参碱结肠靶向微丸仍具有结肠靶向性。     

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。     

卡托普利缓释微丸的制备及处方因素考察

目的:制备卡托普利缓释微丸,并对其处方工艺因素进行考察。方法:选用尤特奇RS 30 D与尤特奇RL 30 D的混合物作为包农缓释材料,采用溶液层积法、流化床底喷方式,进行空白丸芯的上药和缓释包衣;并考察缓释聚合物尤特奇RS 30D与尤特奇RL 30D的不同比例、包衣增重,以及增塑剂用量对药物释放的影响。结果:当尤特奇RS 30D与尤特奇RL 30D的比例为4:1,包衣增重为10%,增塑剂用量为20%时,所制得的缓释微丸具有较好的缓释效果,在1、4和8 h的累积释放率分别为标示量的20%～35%,40%～65%和75%以上。结论:通过调整尤特奇RS 30D与尤特奇RL 30D之间的比例,或提高聚合物包衣增重等手段,能使卡托普利栽药微丸具备较理想的缓释效果。     

头孢呋辛酯掩味微丸的制备

目的:制备头孢呋辛酯掩味微丸。方法:采用离心造粒粉末层积法制备头孢呋辛酯含药素丸,在此基础上进行水分散体掩味包衣,并测定制剂体外溶出度。结果:所得含药微丸40～50目,收率为89.5%,载药量为6.29%,45min时的溶出度达到80%。结论:采用水分散体包衣成功地制备了头孢呋辛酯掩味微丸。     

对黄连提取物进行掩味技术的研究

目的:研究黄连提取物掩味技术。方法:在考察黄连提取物的具体方法及溶剂时将盐酸小檗碱含量当作主要指标,选择提取方法,在掩味处理提取物时主要应用包衣法。结果:提取时应用50%乙醇回流,黄连提取物颗粒包衣液制备材料用PEG6000与丙烯酸树脂Ⅱ号,70:15:15为包衣材料、增塑剂以及抗静电剂比例,经掩味后有较好口感。结论:采用上述技术掩味黄连提取物简单且便于操作,实用性高。     

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.     

氧化苦参碱肠溶包衣微丸的制备

目的:制备氧化苦参碱肠溶包衣微丸。方法:采用单因素试验考察包衣锅转速、包衣锅温度和喷枪压力对包衣条件的影响,并比较各种树脂包衣液的性质,选出适宜的包衣材料;采用包衣锅法制备微丸;以体外释放度评价包衣效果。结果:包衣条件为包衣锅转速50r.min-1、包衣温度30℃、喷枪压力0.10MPa;包衣材料为湖州Ⅲ号聚丙烯酸树脂;制备的微丸体外释放度符合2005年版《中国药典》(二部)要求。结论:所选方法可制备出体外释放良好的氧化苦参碱肠溶包衣微丸。     

Design of taste masked enteric orodispersible tablets of diclofenac sodium by applying fluid bed coating technology

Diclofenac sodium (DS) a non-steroidal anti-inflammatory drug has a bitter taste and is a local stomach irritant. The aim of this study was to formulate taste masked DS orally dispersible tablets (ODTs) with targeted drug release in the intestine. Pellets of DS were designed using sugar sphere cores layered with DS followed by an enteric coat of Eudragit L100 and a second coat of Eudragit E100 for taste masking. The produced pellets had a high loading efficiency of 99.52% with diameters ranging from 493.7 to 638.9?µm. The prepared pellets were spherical with smooth surfaces on scanning electron microscopy examination. Pellets with the 12% enteric coat Eudragit L100 followed by 5% Eudragit E 100 resulted in 1.4?±?0.5% DS release in simulated gastric fluid (SGF) and complete dissolution in simulated intestinal fluid (SIF). The pellets were then used to formulate ODTs. In vitro disintegration time of ODTs ranged from 20?±?0.26 to 46?±?0.27?s in simulated saliva fluid (SSF). Dissolution was less than 10% in SGF while complete drug release occurred in SIF. The release rate was higher for the optimized formulation (F12) in SIF than for the marketed product Voltaren® 25?mg tablets. The optimized ODTs formulation had a palatable highly acceptable taste.     

Optimization of methacrylic acid ester copolymers blends as controlled release coatings using response surface methodology

The aim of this study was to statistically optimize the use of blends of methacrylic acid ester copolymers with different permeability properties as controlled-release coating systems for tablets to produce predictable predesigned release profiles. A full factorial design was used to study and optimize the use of methacrylic acid ester copolymers Eudragit RS 30D and Eudragit RL 30D as coating materials for controlled release. Directly compressed theophylline tablets were coated with aqueous dispersions containing different proportions of the two copolymers using a side-vented coating pan (Accela Cota). The effect of polymer loading level at 5, 7.5, and 10% weight gain and curing time at 50 degrees C for 12 and 24 hours were also evaluated. Coated tablets were tested for their drug release in water using a United States Pharmacopeia (USP) dissolution apparatus #2. The results showed that increasing the content of the lower permeability copolymer Eudragit RS 30D, increasing the polymer load, and increasing curing time at 50 degrees C resulted in slower drug release. A statistical model that describes and predicts the drug release properties of the coated tablets as a function of the copolymers ratio in the coating dispersion, polymer load, and curing time at 50 degrees C was developed. The most significant factor affecting drug release was found to be the ratio of the two copolymers in the coating dispersion followed by the curing time at 50 degrees C and the polymer loading level. Good correlations were observed between the model fitted values andthe experimental values. An optimized formula prepared by superimposing two-dimensional contour plots was prepared; its release profile was found to be in agreement with the prediction obtained from the model.     

盐酸文拉法辛缓释微丸的制备及体外释放度试验

目的制备盐酸文拉法辛缓释微丸,并对其体外释药行为进行研究。方法先用文拉法辛溶液对空白微丸进行上药,通过EC包衣制得速释微丸,然后用速释微丸为丸芯,用EudragitEudragitNE30D,水分散体为包衣材料制备缓释微丸,再将速释微丸和缓释微丸以1:2的比例混合得到最后的缓释微丸。并分别考察了包衣增重对体外释药行为的影响。结果对制备过程中不同阶段的微丸进行了体外释放研究,表明增重20%,速释微丸和缓释微丸以1:2的比例配比结果最为理想。结论盐酸文拉法辛缓释微丸具有较好的释药性能及良好的缓释效果。     

Formulation and in vitro evaluation of ketoprofen fast-dissolving tablets

Drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated as orally fast-disintegrating tablets (FDTs or ODTs). Therefore, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Despite advances in the FDT technologies, formulation of drugs with a bitter taste is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model bitter taste drug; ketoprofen, without affecting the fast-disintegrating properties of the formulation. The unpleasant taste of the active drug usually masked by adding flavoring ingredients and sweeteners to improve taste and palatability but in this study a novel approach of using a polymer; Eudragit EPO and a granulation procedure of this polymer with the active drug was applied to mask the bitter taste of ketoprofen. In order to produce ketoprofen FDT formulations, a two-stepped procedure was followed; granulation process with the taste-masking agent (Eudragit EPO) and then direct compression (F3 and F4). In F1 and F2 formulations, granulation process was not implemented in order to observe the effect of application method of Eudragit EPO. As well as observing the effect of taste-masking agent, crospovidone and sodium starch glycolate were used in different concentrations (2, 4 and 8wt%) to examine the influence of superdisintegrants on FDT properties. All the FDTs containing 30?mg ketoprofen (F1, F2, F3 and F4) were evaluated by means of in vitro quality control tests.     

盐酸二甲双胍缓释微丸的制备及体外释放度考察

目的:制备盐酸二甲双胍(metformin hydrochloride,MH)缓释微丸,并考察其体外释药行为。方法:通过离心造粒法制得MH微丸,以乙基纤维素水分散体(Surelease),丙烯酸树脂水分散体(EudragitNE30D,RS30D)作为膜控释包衣材料,通过流化床包衣制备MH缓释微丸,并考察不同包衣材料、包衣增重、固化时间、释放介质对释放度的影响。结果:离心造粒制得微丸圆整度好,有一定强度,适合包衣,Surelease包衣增重11%时所得的缓释微丸在12 h具有明显的缓释效果,不受释放介质的影响,为零级释放,且12 h释放可以达到85%以上。释放机制主要是通过无孔膜扩散作用。结论:通过离心造粒并用Surelease包衣的MH缓释微丸缓释效果明显,且为零级释放。     

In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit FS 30 D-coated pellets

The objective of this study was to develop meloxicam-loaded colon-specific pellets coated with Eudragit FS 30 D and further evaluate their in vitro release and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading, 4.8%, w/w) were prepared by layering drug-binder (HPMC)-solubilizer (beta-cyclodextrin) solution onto nonpareils (710-850 microm) and then coated with a copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form and a smooth surface with coating thickness approximately 28 microm. The in vitro drug release from the pellets was pH-dependent with sufficient gastric resistance (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3 h incubation). In vivo study was carried out using pentagastrin-pretreated beagle dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w) Eudragit FS 30 D (3.0+/-0.8 h) was significantly delayed (p<0.05) compared to that from the uncoated drug-layered cores (0.6+/-0.3 h). The area under the meloxicam plasma concentration-time curve (AUC(0-->96)(h) was not significantly different between the two preparations (p>0.05), although AUC(0-->96)(h) obtained after oral administration of coated pellets (142.5+/-59.6 microg h/ml) was lower than that obtained after administration of uncoated drug-layered cores (180.8+/-61.9 microg h/ml). These results suggested that meloxicam could be delivered to the colon with 15% (w/w) coating level of Eudragit FS 30 D and this polymer coating had no significant influence on the relative bioavailability of meloxicam of the pellets.     

复方盐酸伪麻黄碱缓释微丸的制备及其释放度考察

目的制备含萘普生钠和盐酸伪麻黄碱的复方缓释微丸,考察理论聚合物包覆量、抗黏剂用量、热处理时间等因素对盐酸伪麻黄碱缓释微丸释放度的影响。方法采用挤出滚圆法制备萘普生钠速释微丸及盐酸伪麻黄碱含药丸芯,采用丙烯酸树脂水分散体(EudragitRS 30D)流化床包衣技术制备盐酸伪麻黄碱缓释微丸,采用紫外分光光度法测定萘普生钠的含量及溶出度,采用HPLC法测定盐酸伪麻黄碱的含量及释放度。结果萘普生钠、微晶纤维素、硫酸钠质量比为10∶9∶1时,制得的萘普生钠速释微丸圆整度好,脆碎度低,10 min累积释药大于90%;当盐酸伪麻黄碱缓释微丸的理论聚合物包覆量为50%、滑石粉用量为聚合物质量的40%、热处理时间为24 h时,药物释放过程接近零级释药模型。结论所制备的萘普生钠速释微丸及盐酸伪麻黄碱缓释微丸体外释药均符合速释和缓释要求,后者的体外释药过程接近零级释药模型。     

Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets.

In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets.