Cheng Bingchao, Li Dongyang, Huo Qiye, Zhao Qianqian, Lan Qi, Cui Mengsuo, Pan Weisan, Yang Xinggang
Department of Pharmaceutics, School of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road 110016, Shenyang, China.
State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, 222001, Jiangsu, Lianyungang, China.
Asian J Pharm Sci. 2018 Mar;13(2):120-130. doi: 10.1016/j.ajps.2017.10.003. Epub 2017 Oct 26.
To obtain expected rapid-release and sustained-release of ketoprofen gel beads, this paper adopted biopolymer alginate to prepare alginate beads and chitosan-alginate gel beads. Formulation factors were investigated and optimized by the single factor test. The release of ketoprofen from calcium alginate gel beads in pH 1.0 hydrochloric acid solution was less than 10% during 2 h, then in pH6.8 was about 95% during 45 min, which met the requirements of rapid-release preparations. However, the drug release of chitosan-alginate gel beads in pH1.0 was less than 5% during 2 h, then in pH6.8 was about 50% during 6 h and reached more than 95% during 12 h, which had a good sustained-release behavior. In addition, the release kinetics of keteprofen from the calcium alginate gel beads fitted well with the Korsmeyer-Peppas model and followed a case-II transport mechanism. However, the release of keteprofen from the chitosan-alginate gel beads exhibited a non-Fickian mechanism and based on the mixed mechanisms of diffusion and polymer relaxation from chitosan-alginate beads. In a word, alginate gel beads of ketoprofen were instant analgesic, while chitosan-alginate gel beads could control the release of ketoprofen during gastro-intestinal tract and prolong the drug's action time.
为实现酮洛芬凝胶珠的预期速释和缓释效果，本文采用生物聚合物海藻酸盐制备海藻酸盐珠和壳聚糖 - 海藻酸盐凝胶珠。通过单因素试验对配方因素进行了研究和优化。酮洛芬从海藻酸钙凝胶珠在pH 1.0盐酸溶液中2小时内的释放量小于10%，然后在pH 6.8时45分钟内约为95%，符合速释制剂的要求。然而，壳聚糖 - 海藻酸盐凝胶珠在pH 1.0时2小时内的药物释放量小于5%，然后在pH 6.8时6小时内约为50%，12小时内达到95%以上，具有良好的缓释行为。此外，酮洛芬从海藻酸钙凝胶珠的释放动力学与Korsmeyer - Peppas模型拟合良好，遵循Ⅱ型转运机制。然而，酮洛芬从壳聚糖 - 海藻酸盐凝胶珠的释放表现出非菲克扩散机制，基于壳聚糖 - 海藻酸盐珠的扩散和聚合物松弛的混合机制。总之，酮洛芬海藻酸盐凝胶珠具有即时镇痛作用，而壳聚糖 - 海藻酸盐凝胶珠可在胃肠道控制酮洛芬的释放并延长药物作用时间。
