Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt.
Saudi Pharm J. 2013 Jan;21(1):61-9. doi: 10.1016/j.jsps.2011.08.004. Epub 2011 Sep 8.
Emulsification/internal gelation has been suggested as an alternative to extrusion/external gelation in the encapsulation of several compounds including non-steroidal anti-inflammatory drugs such as diclofenac sodium. The objective of the present study was a trial to formulate diclofenac sodium as controlled release microparticles that might be administered once or twice daily. This could be achieved via emulsification/internal gelation technique applying Box-Behnken design to choose these formulae. Box-Behnken design determined fifteen formulae containing specified amounts of the independent variables, which included stirring speed in rpm (X1), drug:polymer ratio (X2) and the surfactant span 80% (X3). The dependent variables studied were cumulative percent release after two hours (Y1), four hours (Y2) and eight hours (Y3). The prepared microparticles were characterized for their production yield, sizes, shapes and morphology, entrapment efficiency and Diclofenac sodium in vitro release as well. The results showed that the production yield of the prepared diclofenac sodium microparticles was found to be between 79.55% and 97.41%. The formulated microparticles exhibited acceptable drug content values that lie in the range 66.20-96.36%. Also, the data obtained revealed that increasing the mixing speed (X1) generally resulted in decreased microparticle size. In addition, scanning electron microscope images of the microparticles illustrated that the formula contains lower span concentration (1%) in combination with lower stirring speed (200 rpm) which showed wrinkled, but smooth surfaces. However, by increasing surfactant concentration, microspheres' surfaces become smoother and slightly porous. Kinetic treatment of the in vitro release from drug-loaded microparticles indicated that the zero order is the drug release mechanism for the most formulae.
乳化/内凝胶法已被提议作为挤出/外凝胶法的替代方法，用于包封几种化合物，包括非甾体抗炎药如双氯芬酸钠。本研究的目的是尝试将双氯芬酸钠制成控释微球，每日给药一次或两次。这可以通过乳化/内凝胶技术来实现，应用 Box-Behnken 设计来选择这些配方。Box-Behnken 设计确定了包含特定独立变量的十五种配方，这些变量包括转速 rpm（X1）、药物：聚合物比（X2）和表面活性剂 Span 80%（X3）。研究的因变量是两小时（Y1）、四小时（Y2）和八小时（Y3）后的累积释放百分比。所制备的微球的特征在于产率、粒径、形状和形态、包封效率以及双氯芬酸钠的体外释放。结果表明，所制备的双氯芬酸钠微球的产率在 79.55%至 97.41%之间。所制定的微球表现出可接受的药物含量值，其范围为 66.20-96.36%。此外，所得数据表明，增加混合速度（X1）通常会导致微球粒径减小。此外，微球的扫描电子显微镜图像表明，该配方含有较低的 Span 浓度（1%）与较低的搅拌速度（200rpm）结合使用，其显示出皱缩但光滑的表面。然而，通过增加表面活性剂浓度，微球的表面变得更加光滑且略微多孔。载药微球体外释放的动力学处理表明，对于大多数配方，零级是药物释放机制。
