Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon
Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon
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DOI：
10.1016/j.ijpharm.2007.02.015
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发表时间：
2007-06-29
影响因子：
5.8
通讯作者：
Lin, Senshang
中科院分区：
文献类型：
--
作者：
Krishnamachari, Yogita;Madan, Parshotam;Lin, Senshang
开发了一种微粒系统，该系统由非酶促降解聚（dl-丙交酯-乙交酯）（PLGA）核心组成，并将布地奈德位点特异性递送至远端回肠和结肠。使用溶剂蒸发技术制备负载布地奈德的微粒，研究的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 Eudragit (R) S-100（一种肠溶聚合物）在负载布地奈德的 PLGA 微粒表面形成涂层，用于特定位点递送至远端回肠和结肠。由不同配方参数制备的负载布地奈德的PLGA微粒显示出平均包封率在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，初始释放较高，随后药物释放较慢。增加聚合物和表面活性剂浓度表现出鲜明对比的药物释放曲线，增加聚合物浓度导致较低的药物释放，反之亦然。涂有 Eudragit (R) S-100 涂层的布地奈德 PLGA 微粒显示出包封效率降低，并加速体外药物释放。此外，在酸性pH下药物释放完全延迟，并且一旦肠溶聚合物包衣层在较高pH（7.4和6.8）下溶解，就观察到药物从微粒中受控释放。从这项研究的结果来看，采用 PLGA 基质和 Eudragit (R) S-100 涂层的双微囊技术的应用显示出布地奈德在克罗恩病中的位点特异性和受控递送的前景。 (c) 2007 Elsevier B.V. 保留所有权利。
A microparticulate system consisting of non-enzymatic ally 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 (R) 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 35 mu m. 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 (R) 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 (R) S-100 coating shows promise for site specific and controlled delivery of budesonide in Crohn's disease. (c) 2007 Elsevier B.V. All rights reserved.