埃索美拉唑镁肠溶微丸的制备

目的:采用流化床上药包衣技术制备埃索美拉唑镁肠溶微丸。方法:选择含药层药物浓度、隔离层增重、肠衣层增重为影响因素,以肠溶微丸耐酸力和释放度为评价指标,采用Box-Behnken效应面法优化肠溶微丸处方,并对最优处方进行验证。结果:最优处方为上药浓度19.16%,隔离层增重17.15%,肠衣层增重66.15%,优化处方实测值与预测值相近。结论:该处方工艺可行,重复性良好,质量稳定可靠。     

泮托拉唑钠肠溶微丸胶囊的制备

以泮托拉唑钠、聚乙烯吡咯烷酮、滑石粉、磷酸钠、磷酸氢二钠和水混合制成主药层包衣溶液。采用流化床包衣技术,对空白丸芯依次包主药层、隔离层和肠溶层,制得泮托拉唑钠肠溶微丸,并优化了处方和工艺。将所得肠溶微丸装入普通胶囊中制成泮托拉唑钠肠溶微丸胶囊。3批制品在pH 6.8磷酸盐缓冲液中30 min时释放度分别为91.74%、87.98%、88.31%,在0.1 mol/L盐酸中2 h时的耐酸力分别为98.71%、97.18%、101.5%。     

娑罗子肠溶微丸胶囊的制备及质量评价

采用流化床底喷包衣法，对蔗糖丸芯依次包药物层、隔离层和肠溶衣层，制备娑罗子总皂苷提取物肠溶微丸。以微丸上药率、收率、工艺可行性、七叶总皂苷含量及2 h酸中释放量为评价指标，采用单因素试验结合多指标综合评价法优化肠溶微丸处方。照所得优化处方平行制备3批样品，并测得肠溶微丸的平均粒径为665.26μm，堆密度约为0.92 g/mL，脆碎度低于2.5%，总皂苷含量为(101.30±0.79)%。将所得肠溶微丸装入胶囊后进行体外释放度试验。结果显示，该肠溶微丸胶囊的2 h酸中释放量为(5.26±2.25)%，在磷酸盐缓冲液(pH 6.8)介质中45 min时基本释放完全。     

兰索拉唑肠溶微丸的制备及处方优化

目的制备兰索拉唑肠溶微丸。方法采用流化床包衣技术,以空白丸芯为母核,依次包以主药层、隔离层、中性层和肠溶层,制备成兰索拉唑肠溶微丸,并对处方及工艺进行优化。结果按最佳处方工艺制备的3批兰索拉唑肠溶微丸释放度分别为96.4%、94.8%和94.3%。结论本方法制备的兰索拉唑肠溶微丸,工艺可行,质量可靠。     

泮托拉唑钠肠溶微丸的制备

以泮托拉唑钠、羟丙甲纤维素、无水碳酸钠、吐温-80、十二烷基磺酸钠和水混合制成主药层包衣溶液.采用流化床包衣技术,对空白丸芯依次包主药层、隔离层和肠溶层,制得泮托拉唑钠肠溶微丸,并优化了处方和工艺.将所得肠溶微丸装入普通胶囊中制成泮托拉唑钠肠溶微丸胶囊,3批制品在pH 6.8磷酸盐缓冲液中45 min时的释放度分别为(97.6±1.1)%、(98.1±1.3)%、(98.4±1.9)%,在0.1 mol/L盐酸中2h时的释放量分别为(2.9±1.7)%、(2.9±1.4)%、(2.3±2.1)%.     

奥美拉唑肠溶微丸胶囊的制备及质量考察

目的制备奥美拉唑肠溶微丸胶囊。方法用离心制丸法直接制备载药母丸,再用流化床包衣法进行微丸包衣;采用正交试验设计对包衣液处方进行筛选优化,研究玉米朊在隔离层上的应用,采用新的肠溶层包衣处方。结果试验处方制得的奥美拉唑肠溶微丸稳定性好,酸性介质中2 h稳定性良好,耐酸力≥98%,p H 6.8缓冲液中释放达标,45 min体外释放度≥90%。结论采用药丸直接起母的方法简化了操作,降低了成本;选用玉米朊作为隔离层成膜材料,很好地提高了奥美拉唑的稳定性;在肠溶层中采用单硬脂酸甘油酯,既促进了微丸的体外释放,又增强了肠溶衣的稳定性。     

TRH-03肠溶微丸的制备及其处方优化

目的研究TRH-03肠溶微丸的处方优化及制备工艺。方法采用流化床包衣法,以载药量及释放量为考察指标,对TRH-03肠溶微丸的处方、上药和包衣工艺进行了优化。结果制得的3批肠溶微丸圆整度好,其载药率分别为35.63%、35.04%、35.64%;在人工胃液中保持不释药,人工肠液中45min内释放率分别为89.58%、88.96%、88.36%,载药量稳定且重现性好,体外释放度符合中国药典2010年版二部的要求。结论本方法制备工艺简单易行,重复性好,适合进一步的工业化生产。     

粉末层积法和液相层积法制备多西环素肠溶微丸的对比

目的 对比粉末层积法和液相层积法制备盐酸多西环素肠溶微丸.方法 分别采用粉末层积法和液相层积法制备盐酸多西环素载药丸芯,以圆整度、脆碎度、收率等为指标,筛选最优处方和制备工艺,采用流化床液相层积法对载药丸芯进行隔离层和肠溶层包衣.将两种方法制备的肠溶微丸在制备方法、微丸外观及体外药物释放等方面进行比较.结果 两种方法均...     

兰索拉唑肠溶微丸胶囊的制备

目的:制备兰索拉唑肠溶微丸胶囊。方法:采用流化床包衣技术,在空白丸芯上依次包以主药层、隔离层和肠溶层,制备成兰索拉唑肠溶微丸,将肠溶微丸装入普通胶囊制成兰索拉唑肠溶微丸胶囊,并考察3批制剂的载药率及在人工肠液和人工胃液中的释放情况。结果:所制微丸圆整度高,外观亮泽,载药均匀、载药率高(平均值在96%以上),包衣效果好;其在人工肠液中45min的体外累积释放率大于(94.3±0.76)%,在人工胃液中2h的释放量小于(6.2±1.6)%。结论:所制兰索拉唑肠溶微丸胶囊工艺可行,重现性良好,质量稳定可靠,具有良好的体外释药性和耐酸力。     

右旋雷贝拉唑钠肠溶微丸的制备及体外释放度考察

目的:制备右旋雷贝拉唑钠肠溶微丸,并考察其体外释放度。方法:采用流化床底喷包衣技术制备右旋雷贝拉唑钠上药微丸,再用HPMC E5包隔离衣,最后使用丙烯酸树脂L30D-55包肠溶衣,制成右旋雷贝拉唑钠肠溶微丸。并比较自研制剂与参比制剂体外释放度的相似性。结果:右旋雷贝拉唑钠肠溶微丸包衣处方为:HPMC E5隔离衣层增重为12.0%,丙烯酸树脂L30D-55肠溶衣层增重为45.0%,增塑剂用量为聚合物重量的8.0%。体外释放度结果显示,自研制剂和参比制剂f₂相似因子大于50,说明两种制剂体外释放行为相似。结论:制备的右旋雷贝拉唑钠肠溶微丸的释药行为较好,有望应用于工业生产。     

Preparation and optimization of various parameters of enteric coated pellets using the Taguchi L9 orthogonal array design and their characterization

Duloxetine hydrochloride enteric coated pellets were formulated using fluidized bed. Three separate layers, the drug layer, the barrier layer, and the enteric layer, were coated onto the inert core pellets. The pellets were optimized with the acid resistance and drug release in simulated intestinal fluid as the process parameters, using the Taguchi L9 orthogonal array. Various other properties, such as surface morphology, bulk and tapped density, Hausner's ratio, hardness, friability, yield of pellets, moisture content, and particle size distribution, were also studied in the optimized pellets. The concentration of the enteric polymer played a vital role in acid resistance, while the type of enteric polymer affected the drug release in simulated intestinal fluid. In both cases, it was determined that binder polymer concentration was not affected much. The comparisons between the optimized pellets and a market formulation yielded f1 and f2 values within a range of 4–5 and 60–65, respectively. Three month stability studies, conducted at accelerated conditions, showed the optimized pellets to be stable. Taguchi plays an important role in optimizing parameters, and optimization of duloxetine hydrochloride can be achieved with minimal trials.     

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...     

右旋酮洛芬肠溶微丸的研制及其体外释放研究

目的：制备右旋酮洛芬肠溶微丸,并考察其在0.1 mol·L-1盐酸溶液和pH 6.8磷酸缓冲液（PBS）中的释放情况。方法：采用流化床包衣技术,在空白糖丸芯上依次包主药层、隔离层和肠溶衣层,制备成肠溶衣微丸;以上药率为指标,考察HPMC浓度和主药上药浓度;观察是否粘连、颗粒大小均一度和表面色泽均匀与否等综合指标,采用正交试验优选包衣工艺条件;与普通肠溶片比较在PBS中的释放情况。结果：制得的微丸上药均匀、上药率高、外观圆整有光泽;确定HPMC浓度和主药上药浓度分别为5%和15%,优选出最佳包衣工艺条件为物料温度为36℃、雾化压力为1.0 bar及喷枪速度为0.8 ml·min-1;在盐酸溶液中2 h的释放量小于10%,在PBS中的释放度高于普通肠溶片。结论：所制右旋酮洛芬肠溶微丸工艺可行,具有良好的耐酸性和体外释放度。     

盐酸可乐定脉冲释药微丸的制备工艺研究

目的研究盐酸可乐定脉冲释药微丸的制备方法。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。结果各考察因素均对药物的释放影响显著。优选工艺结果为,含药丸芯采用微晶纤维素,溶胀层材料采用低取代羟丙纤维素,控释层采用乙基纤维素水分散体,溶胀层和控释层包衣增重分别为10％和15％。制备的微丸时滞时间为4．2h左右,时滞后1h内累积释药百分率达到90％。结论盐酸可乐定微丸在体外具有有脉冲释药特性。     

盐酸地尔硫卓延迟缓释微丸的制备及处方优化

目的制备盐酸地尔硫卓延迟缓释微丸并对其处方进行优化。方法采用挤出滚圆法制备含药丸芯。采用流化床双层包衣技术以乙基纤维素为内层包衣材料,乙基纤维素与丙烯酸树脂的混合膜材为外层包衣材料制备延迟缓释微丸。以释放度为考察指标对其进行单因素考察,采用星点设计-效应面法优化处方,并对模型处方进行验证。结果单因素考察结果表明内层包衣增重、外层包衣增重以及外层包衣材料配比对释放度影响显著。通过所建立优化模型的效应面图可知,内层包衣增重X1=4.5%⁷.0%,外层包衣增重X2=7.0%7.0%,外层包衣增重X2=7.0%¹8.5%时所得的模型处方具有理想的释放时滞和释药速率。处方验证结果的f2相似因子为69.24>50,表明3批自制微丸的释药曲线与理论释药曲线具有良好的相似性。结论制备了具有理想释药时滞和释药速率的盐酸地尔硫卓延迟缓释微丸,所建数学模型具有良好的预测效果。     

丹参素缓释微丸的制备及家兔体内药动学研究

目的:制备丹参素24 h缓释微丸并研究其在家兔体内的药动学行为。方法:采用挤出滚圆法制备丹参素含药丸芯,以尤特奇水分散体为缓释包衣材料进行流化床包衣制备缓释微丸,研究制剂在家兔体内药动学行为。结果:所得丹参素缓释微丸圆整度好,包衣均匀,体外达到24 h缓慢释放。家兔口服相同剂量的丹参素速释微丸和缓释微丸后,Cmax分别为(1.45±0.24)μg·mL-1和(0.67±0.13)μg·mL-1,Tmax分别为(2.00±0.30)h和(8.00±0.50)h,MRT分别为(3.50±0.25)h和(10.93±0.26)h。与丹参素速释微丸相比缓释微丸的相对生物利用度为111.28%±1.28%。结论:丹参素缓释微丸可以达到24 h缓释,以AUC为评价指标时,与丹参素速释微丸生物等效。     

结肠定位释药瓜尔胶/乙基纤维素包衣小丸

体外研究瓜尔胶/乙基纤维素混合包衣小丸的结肠靶向性。以5-氟尿嘧啶为模型药， 采用流化包衣技术以瓜尔胶/乙基纤维素混合物的水/醇混悬液对载药小丸进行喷液包衣。瓜尔胶/乙基纤维素混合包衣小丸的释药行为取决于包衣处方中瓜尔胶与乙基纤维素的比例和包衣厚度。分别以混合包衣液中瓜尔胶与乙基纤维素的比例及包衣增重为自变量， 以T₅和T₉₀（药物释放5%和90%所需要的时间）为效应， 进行3×4析因设计/效应面优化， 筛选较优处方。结果表明随着乙基纤维素在衣层中所占比例的增大及包衣厚度的增加， 药物释放时滞增加。当瓜尔胶与乙基纤维素的比例在0.2~0.7， 并且包衣增重在250%~500%时， T_5%为5.1～7.8 h， T_90%为9.8～16.3 h。并且在释药时滞之后， 进入模拟结肠微菌群酶解作用的释放环境中(pH 6.5)药物释放速度加快， T_90%缩短到9.0～14.5 h。由此可以看出适当的瓜尔胶/乙基纤维素混合衣层既可以保护药物顺利通过上消化道而不释放， 达到结肠后药物开始释放， 并且可在结肠微菌群的酶解作用下加速药物的释放， 实现结肠定位释药的目的。     

Properties of enteric coated sodium valproate pellets

The influence of subcoat application and micro-environmental pH on the dissolution properties of enteric coated sodium valproate pellets was investigated. The pellets were prepared by solution-layering or wet-mass extrusion-spheronization methods. In order to pass the USP enteric test, the solution-layered and wet-mass extruded pellets required 35 and 25% weight gain of Eudragit L 30D-55, respectively. The application of a subcoat of either Methocel-E5 (HPMC) or Opadry AMB to the pellets resulted in a delay in sodium valproate release in 0.1N HCl. Further delay in drug release was observed when citric acid was present in a HPMC subcoat or when added to the core pellet formulation. The amount of drug released from coated pellets was a function of the level of citric acid in the pellet core or subcoat and subsequent micro-environmental pH of the pellets. Citric acid exerted a plasticizing effect on the enteric polymer film and improved film formation and polymer coalescence. When greater than 10% (w/w) citric acid was present in the pellets, a decrease in drug content was observed due to the conversion of sodium valproate to the volatile compound, valproic acid. Pellets containing less than 10% (w/w) citric acid maintained potency during processing.     

Development of a novel osmotically driven drug delivery system for weakly basic drugs

The drug substance SAG/ZK has a short biological half-life and because of its weakly basic nature a strong pH-dependent solubility was observed. The aim of this study was to develop a controlled release (cr) multiple unit pellet formulation for SAG/ZK with pH-independent drug release. Pellets with a drug load of 60% were prepared by extrusion/spheronization followed by cr-film coating with an extended release polyvinyl acetate/polyvinyl pyrrolidone dispersion (Kollidon SR 30 D). To overcome the problem of pH-dependent drug release the pellets were then coated with a second layer of an enteric methacrylic acid and ethyl acrylate copolymer (Kollicoat MAE 30 DP). To increase the drug release rates from the double layered cr-pellets different osmotically active ionic (sodium and potassium chloride) and nonionic (sucrose) additives were incorporated into the pellet core. Drug release studies were performed in media of different osmotic pressure to clarify the main release mechanism. Extended release coated pellets of SAG/ZK demonstrated pH-dependent drug release. Applying a second enteric coat on top of the extended release film coat failed in order to achieve pH-independent drug release. Already low enteric polymer levels on top of the extended release coated pellets decreased drug release rates at pH 1 drastically, thus resulting in a reversal of the pH-dependency (faster release at pH 6.8 than in 0.1N HCl). The addition of osmotically active ingredients (sodium and potassium chloride, and sucrose) increased the imbibing of aqueous fluids into the pellet cores thus providing a saturated drug solution inside the beads and increasing drug concentration gradients. In addition, for these pellets increased formation of pores and cracks in the polymer coating was observed. Hence drug release rates from double layered beads increased significantly. Therefore, pH-independent osmotically driven SAG/ZK release was achieved from pellets containing osmotically active ingredients and coated with an extended and enteric polymer. In contrast, with increasing osmotic pressure of the dissolution medium the in vitro drug release rates decreased significantly.