Krishnamachari Yogita, Madan Parshotam, Lin Senshang
College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, United States.
Int J Pharm. 2007 Jun 29;338(1-2):238-47. doi: 10.1016/j.ijpharm.2007.02.015. Epub 2007 Feb 16.
A microparticulate system consisting of non-enzymatically degrading poly(dl-lactide-co-glycolide) (PLGA) core and delivering budesonide site specifically to distal ileum and colon was developed. Budesonide-loaded microparticles were fabricated using solvent evaporation technique and formulation variables studied included different molecular weight grades of PLGA polymer as well as concentration of polymer, surfactant and drug. Eudragit S-100, an enteric polymer, was then used to form a coating on the surface of budesonide-loaded PLGA microparticles for site specific delivery to the distal ileum and colon. Budesonide-loaded PLGA microparticles prepared from various formulation parameters showed mean encapsulation efficiencies ranging between 50% and 85% and mean particle size ranging between 10 and 35mum. In vitro release kinetics studies showed a biphasic release pattern with an initial higher release followed by a slower drug release. Increasing polymer and surfactant concentrations exhibited sharply contrasting drug release profiles, with increasing polymer concentrations resulting in a lower drug release and vice versa. The budesonide-loaded PLGA microparticles coated with Eudragit S-100 coating showed a decrease in entrapment efficiency with an accelerated in vitro drug release. Moreover, complete retardation of drug release in an acidic pH, and, once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microparticles were observed. From the results of this investigation, the application of double microencapsulation technique employing PLGA matrix and Eudragit S-100 coating shows promise for site specific and controlled delivery of budesonide in Crohn's disease.
研发了一种微粒系统，其由非酶降解的聚（dl-丙交酯-共-乙交酯）（PLGA）核组成，可将布地奈德特异性递送至回肠末端和结肠。采用溶剂蒸发技术制备了载布地奈德微粒，并研究了配方变量，包括不同分子量等级的PLGA聚合物以及聚合物、表面活性剂和药物的浓度。然后使用肠溶聚合物Eudragit S-100在载布地奈德的PLGA微粒表面形成涂层，以实现向回肠末端和结肠的特异性递送。由各种配方参数制备的载布地奈德PLGA微粒的平均包封率在50%至85%之间，平均粒径在10至35μm之间。体外释放动力学研究显示出双相释放模式，最初释放较快，随后药物释放较慢。聚合物和表面活性剂浓度的增加呈现出截然不同的药物释放曲线，聚合物浓度增加导致药物释放降低，反之亦然。涂有Eudragit S-100涂层的载布地奈德PLGA微粒的包封率降低，体外药物释放加速。此外，在酸性pH值下药物释放完全延迟，并且一旦肠溶聚合物涂层在较高pH值（7.4和6.8）下溶解，就会观察到药物从微粒中控制释放。从这项研究的结果来看，采用PLGA基质和Eudragit S-100涂层的双重微囊化技术在克罗恩病中对布地奈德进行特异性和控释显示出前景。
