复方盐酸伪麻黄碱镶嵌缓释片的制备及其体外释放度的测定

目的　制备盐酸伪麻黄碱和萘普生钠复方镶嵌缓释片,并研究其体外释放特性。方法　以亲水凝胶(ＨＰＭＣＫ100Ｍ)为缓释部分基质,采用二次压片的工艺研制了盐酸伪麻黄碱和萘普生钠复方镶嵌缓释片;以磷酸盐缓冲液(ｐＨ7.2)为释放介质,采用紫外分光光度法和酸性染料比色法分别测定了释放液中萘普生钠和盐酸伪麻黄碱的含量,并计算其体外释放度。结果　自制盐酸伪麻黄碱和萘普生钠复方镶嵌缓释片中萘普生钠在0 .5ｈ的释放量大于75%,盐酸伪麻黄碱在0 5ｈ的累积释放约7%±3. 6%,1ｈ为15. 8%±2 .3%,4ｈ为49 .5%±3 .9%,8ｈ在85%以上。结论　该复方镶嵌缓释片兼具速释和缓释特点,效果显著。     

盐酸美金刚缓释微丸的制备及体外释放度考察

目的:制备盐酸美金刚缓释微丸,并对其体外释放度进行考察。方法:采用流化床包衣法制备盐酸美金刚载药微丸,再用Eudragit RL 30D和Eudragit RS 30D进行包衣,制成盐酸美金刚缓释微丸,并考察盐酸美金刚缓释微丸的体外释药行为。结果:体外释放度试验显示,制备的盐酸美金刚缓释微丸在24 h内平稳释放且释药完全,释药规律符合零级释药模型。结论:用本方法制备的盐酸美金刚缓释微丸具有缓释效果。     

萘普生肠溶微丸的制备及其体外特性研究

目的:研制萘普生肠溶微丸,评价其体外释药特性.方法:采用丸芯上药法制备萘普生含药微丸,以丙烯酸II号树脂为衣材进行包衣,采用释放度试验考察萘普生肠溶微丸的体外释药特性,并进行了稳定性试验.结果:本品在pH1.2盐酸溶液中2 h的溶出量低于10%,在pH6.8磷酸缓冲液中可迅速释放药物,45 min累积溶出量可达80%以上.结论:用丙烯酸Ⅱ号树脂为衣材制备萘普生肠溶微丸工艺可行,质量可靠.     

盐酸伪麻黄碱和萘普生复方镶嵌缓释片及其释药规律研究

目的:研究盐酸伪麻黄碱与萘普生复方镶嵌缓释片及其释药规律。方法:在剂型设计上萘普生以常规方式快速释放,盐酸伪麻黄碱以缓释方式释放,以使该制剂适用于1～2次·d~(-1)给药。采用高效液相色谱法对盐酸伪麻黄碱和萘普生同时进行片剂释放度和含量的测定。为考察镶嵌片的释药规律,以释放度为指标,引用Lapidus-Lordi释药方程与初选处方的释药曲线拟合,考察其拟合度。结果:中试样品测定,符合《中华人民共和国药典》2005年版的要求。色谱条件具有较好的专属性、灵敏度和准确度。释药曲线与Lapidus-Lordi释药方程有较好拟合度(r=0.9980)。结论:盐酸伪麻黄碱和萘普生复方镶嵌缓释片的处方剂型可行,Lapidus-Lordi释药方程可以作为处方筛选的一个理论模型。     

熔融高速搅拌法制备双氯芬酸钠缓释胶囊的研究

目的研究熔融高速搅拌法制备双氯芬酸钠缓释胶囊及其体外释药行为。方法采用KJZ-10型熔融高速搅拌制粒机制备含药微丸,以微丸体外释放度为指标,考察处方工艺因素对微丸体外释放度的影响,通过释放度曲线药动力学拟合确定微丸缓释机制。结果双氯芬酸钠微丸体外释放行为符合Higuchi方程Y=35.43t1/2-16.1523（r=0.9988）,释药机制主要是骨架溶蚀和扩散释放。结论该技术制备的双氯芬酸钠缓释微丸具有较好的释药性能及良好的缓释效果。     

萘普生钠伪麻黄碱缓释片的处方工艺研究及体外释放度考察

目的研究萘普生钠伪麻黄碱缓释片的制备方法,筛选出最佳处方制备工艺条件。方法采用正交设计,以HPMC K15M、微晶纤维素(PH101)和乳糖的用量及缓释片的硬度为因素进行试验,确定出最佳制备工艺条件;并对优化的试验结果进行验证,同时考察其体外释放效果。结果缓释层最佳工艺条件:HPMC K15M、PH101、乳糖的用量分别为150mg、40mg、60mg,压片硬度8kg;所制备的样品在1、2、4h的体外累积释放率分别为43.62±1.81%、68.81±1.52%、95.22±1.07%。结论制备的萘普生钠伪麻黄碱缓释片的缓释效果与设计值基本吻合,工艺重现性好,体外累积释放率符合要求。关键词:萘普生钠盐酸伪麻黄碱双层缓释片正交试验设计制备工艺体外累积释放率     

正交试验法研制萘普生缓释微丸

目的　研究萘普生缓释微丸的制备,减小给药次数,降低不良反应。方法　采用正交试验法进行萘普生缓释微丸的工艺研究。结果　体外释放度试验中, 8h累积释放量大于75%,释放行为符合Higuchi方程,本品在加速稳定性试验条件下较为稳定。结论　该缓释微丸处方合理,工艺简单,有理想的缓释效果。     

盐酸普拉克索缓释微丸的制备及体外释放度考察

目的:制备盐酸普拉克索缓释微丸。方法:采用挤出-滚圆法制备盐酸普拉克索微丸,再用EudragitRL30D和EudragitRS30D进行包衣,最终制成盐酸普拉克索缓释微丸,并用高效液相色谱法测定药物含量。结果:体外释放度实验显示,制备的盐酸普拉克索缓释微丸在24 h内平稳释放且释药完全。结论:用本方法制备的盐酸普拉克索缓释微丸体外释药平稳,释药规律符合一级释放模型。     

正交试验法研制萘普生缓释微丸

目的研究萘普生缓释微丸的制备,减小给药次数,降低不良反应.方法采用正交试验法进行萘普生缓释微丸的工艺研究.结果体外释放度试验中,8 h累积释放量大于75%,释放行为符合Higuchi方程,本品在加速稳定性试验条件下较为稳定.结论该缓释微丸处方合理,工艺简单,有理想的缓释效果.     

熔融高速搅拌法制备双氯芬酸钠缓释胶囊的研究

目的 研究熔融高速搅拌法制备双氯芬酸钠缓释胶囊及其体外释药行为。方法 采用KJZ-10型熔融高速搅拌制粒机制备含药微丸,以微丸体外释放度为指标,考察处方工艺因素对微丸体外释放度的影响,通过释放度曲线药动力学拟合确定微丸缓释机制。结果 双氯芬酸钠微丸体外释放行为符合Higuchi方程 Y=35.43t_1/2-16.152 3(r=0.998 8),释药机制主要是骨架溶蚀和扩散释放。结论 该技术制备的双氯芬酸钠缓释微丸具有较好的释药性能及良好的缓释效果。     

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。     

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.     

中心复合设计法优化盐酸伪麻黄碱缓释微丸包衣液处方

目的:采用Eudragit RS30D对盐酸伪麻黄碱微丸进行缓释包衣,优化包衣液处方。方法:通过单因素考察,确定影响药物释放的主要因素,以综合评分值(Y)为评价指标,采用中心复合设计试验对包衣液处方进行优化,确立处方组成,并在优化区域内选择一点安排一次验证试验,以检验优化工艺条件的有效性。结果:理论包衣增重(X1)和抗黏剂滑石粉用量(X2)是影响药物释放的主要因素,其中理论包衣增重(X1)对评价指标有非常显著影响(P<0.01),拟合所得多元二次方程为Y=576.2-17.88X1-4.244X2 0.1449X12 0.06391X1X2 0.01080X22,r=0.9775。验证试验表明,本优化方程有良好的预测性。结论:中心复合设计法优化的制备条件良好,制得的盐酸伪麻黄碱缓释微丸的体外累积释放度符合要求。     

盐酸氨溴索包衣小丸的制备及其释药特性

目的：研制盐酸氨溴索（Amb）包衣小丸，评价其体外释药特性及释药机制。方法：Glatt流化床底喷装置中混悬液法上药制备载药小丸，分别以不同eudragit RS100/eudragit RL100配比为包衣材料制备包衣小丸，释放度试验及扫描电镜考察小丸的体外释药特性及释药机制。结果：包衣小丸在扫描电镜下表面光滑圆整，纵切面层次分明；4种小丸配比而成的缓释胶囊释药曲线与进口缓释胶囊兰勃素差异无显著性，且不受介质pH和转篮转速等因素影响；包衣小丸的释药机制可能为浓度梯度作用下Amb按Fick's定律从完整eudragit膜聚合物链间的分子孔隙扩散。结论：Amb包衣小丸具有理想的缓释效果。     

Influence of film additives on stabilizing drug release rates from pellets coated with acrylic polymers.

The objective of this study was to investigate the influence of talc and triethyl citrate (TEC) on stabilizing the drug release rates following curing and storage at elevated temperature of pellets coated with an aqueous acrylic polymeric dispersion. Core pellets containing anhydrous theophylline (20%), microcrystalline cellulose, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The aqueous dispersions were prepared by adding up to 30% TEC as a plasticizer and talc up to 200% as an antiadherent to a mixture of Eudragit RS 30D/RL 30D (95:5). The theophylline pellets were coated in a fluidized-bed coating unit and then cured at elevated temperatures. Theophylline pellets were successfully coated with the Eudragit dispersions that contained up to 200% talc, based on the dry polymer weight, and the coating efficiency was greater than 93%. Our results demonstrated that the polymer, which was plasticized by TEC, was able to function as a film-forming agent for dispersions containing high levels of talc. No sticking of the coated pellets was observed during the coating process or during the curing or equilibrating phase, even with high levels of TEC in the film. The dissolution rate of theophylline from the coated pellets was delayed when the film coating dispersion contained high levels of talc. Additionally, the stability of the drug release profiles from the coated pellets after storage was significantly improved. Furthermore, a modified dissolution testing used to simulate mechanical stresses that may be encountered in vivo showed the film coated pellets would have sufficient strength. The results of this study demonstrated that high levels of film additives in the acrylic dispersion contributed to the stabilization of the drug release rates as well as the reproducibility of the coating process.     

离心造粒法制备罗红霉素缓释小丸

目的：制备罗红霉素缓释小丸,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罗红霉素含药丸芯,以聚丙烯酸树脂Eudragit NE30D为包衣液制成膜控缓释小丸,考察包衣增重、致孔剂用量等因素对缓释小丸释放度的影响。结果：通过单因素考察确定了包衣液处方,所制备的小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：制备的罗红霉素缓释小丸符合12h缓释要求。     

离心造粒法制备盐酸坦索罗辛缓释微丸胶囊的工艺影响因素及体外释放度考察

目的:制备盐酸坦索罗辛缓释微丸。方法:采用离心造粒粉末层积法制备盐酸坦索罗辛微丸。通过考察主机转速、喷浆泵转速、供粉速度、喷枪雾化条件、抛光时间、包衣增重对微囊收率的影响,确定各因素较佳水平;制备微晶纤维素空白丸芯和盐酸坦索罗辛含药微丸,并在此基础上进行丙烯酸树脂水分散体包衣,对包衣微丸的释药特征进行探讨。结果:微丸成丸的最佳工艺参数为主机转速200r·min-1,喷浆泵转速20r·min-1,供粉速度50r·min-1,喷气压力0.5MPa,喷气流量10～15L·min-1,抛光时间5min,包衣增重11%。3批样品经放大试验,测得微晶纤维素空白丸芯、含药微丸、包衣微丸的收率分别是97.5%、95.4%、96.8%。缓释微丸胶囊体外释药行为较好地符合零级方程。结论:采用离心造粒法在优化的工艺条件下可制得符合要求的盐酸坦索罗辛缓释微丸。     

pH依赖—缓释型美沙拉秦结肠靶向小丸的制备与体外评价

以肠溶型和渗透型丙烯酸树脂为包衣材料制备ｐＨ依赖－缓释型美沙拉秦结肠靶向小丸,评价其体外释放特性。结果表明,包衣小丸在０．１ｍｏｌ／ＬＨＣｌ中２ｈ几乎不释放药物,在ｐＨ７．５缓冲液中具有较好的缓释作用。在模拟胃肠道各区段最高的和最低的ｐ变化的释放度试验中,均在对应小肠区段时开始缓慢释药。分别有４０％和７０％的药物进入结肠后释放。优于单独的肠溶或缓释制剂。     

盐酸伪麻黄碱脉冲小片包衣液处方优化

目的制备盐酸伪麻黄碱脉冲控释小片,并对其体外释药情况进行研究。方法制备盐酸伪麻黄碱含药片芯,采用丙烯酸树脂水分散体(Eudragit(RS 30D)制备盐酸伪麻黄碱脉冲控释小片。通过单因素实验考察药物释放的影响因素,确立处方组成,采用正交设计对包衣液处方进行优化。结果当隔离层增质量分数为2%、控释层增质量分数为5%、CMS-Na用量质量分数为25%,脉冲控释小片的时滞为6 h,体外具有脉冲释药特性。结论成功地制备了盐酸伪麻黄碱脉冲控释小片,体外释药符合脉冲释药的要求。     

盐酸尼卡地平缓释微丸的制备

目的 制备盐酸尼卡地平缓释微丸,并考察其体外释药的影响因素.方法 采用底喷式流化床包衣法,以空白丸芯为基础制备速释微丸,乙基纤维素水分散体为包衣材料制备盐酸尼卡地平缓释微丸,考察其包衣处方及工艺的影响因素.结果 所得缓释微丸在2、6、12h的累积释药百分率分别为24％、69％、87％,体外释放曲线符合一级方程.结论 制备的微丸缓释效果理想,且制备工艺简单,操作方便.