Philip Anil, Pathak Kamla
Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura- 286001, Uttar Pradesh, India.
PDA J Pharm Sci Technol. 2007 Jan-Feb;61(1):24-36.
A non-disintegrating, in situ-formed, asymmetric membrane, polymeric capsular system, offering improved osmotic effect, was used to deliver poorly water-soluble drug in a controlled manner. The poorly water-soluble drug ketoprofen was selected as a model drug to demonstrate how controlled release characteristics can be manipulated by design of in situ-formed polymeric capsule with an asymmetric membrane and core formulations. In situ-formed, asymmetric membrane capsule was made by dry method via precipitation of asymmetric membrane on the walls of hard gelatin capsule. Resulting asymmetric membrane composed of a dense outer region with fewer pores and a lighter inner porous region. The present study evaluates the influence of variables based on two-factor composite design, namely, ethylcellulose and osmogen (sodium chloride), apart from studying effect of varying osmotic pressures of dissolution medium and level of pore-former concentration (glycerol) on drug release. Statistical significance was tested at P < 0.05. Results showed the best formulation (F-5) to closely corresponded to extra design checkpoint formulation by a similarity (f2) value of 95.41 and capsules made with 15% w/v EC, 50 mg sodium chloride, 8% w/v glycerol and 30 mg citric acid (F-11), to achieve therapeutic concentration within first hour of dissolution not observed with any other formulations used in the study. Drug release followed Fickinan diffusion and was independent of pH but dependent on the osmotic pressure of the dissolution medium.
一种非崩解型、原位形成的不对称膜聚合物胶囊系统，具有改善的渗透效果，用于以可控方式递送难溶性药物。选择难溶性药物酮洛芬作为模型药物，以展示如何通过设计具有不对称膜和核心制剂的原位形成聚合物胶囊来控制释放特性。原位形成的不对称膜胶囊通过干法制备，即在硬明胶胶囊壁上沉淀不对称膜。所得不对称膜由孔隙较少的致密外部区域和较疏松的内部多孔区域组成。本研究基于二因素复合设计评估变量的影响，即乙基纤维素和渗透剂（氯化钠），此外还研究了溶出介质渗透压变化和致孔剂浓度（甘油）水平对药物释放的影响。在P < 0.05水平检验统计学显著性。结果显示，最佳制剂（F-5）与额外设计检查点制剂的相似性（f2）值为95.41，与由15% w/v乙基纤维素、50 mg氯化钠、8% w/v甘油和30 mg柠檬酸制成的胶囊（F-11）密切对应，在溶出的第一小时内达到治疗浓度，而该研究中使用的任何其他制剂均未观察到这一情况。药物释放遵循菲克扩散，与pH无关，但取决于溶出介质的渗透压。
