Gong Wei, Liu Yan, Mei Dan-Yu, Yang Meiyan, Mei Xing-Guo
Pharmaceutical Department, Beijing Institute of Pharmacology and Toxicology , Beijing , China and.
Drug Dev Ind Pharm. 2015 Mar;41(3):464-9. doi: 10.3109/03639045.2013.877923. Epub 2014 Jan 9.
Preparation and in vitro/in vivo evaluation of risperidone elementary osmotic pump (RIS-EOP) formulations were investigated. A method for the preparation of RIS-EOP tablets was developed by modulating RIS solubility with citric acid. The influence of osmotic agents and the compositions of semipermeable membrane on drug release profiles was evaluated. The formulation of RIS-EOP was optimized by orthogonal design. The in vitro release profile of the optimum formulation achieved to deliver RIS at an approximate zero-order up to 12 h. The pharmacokinetic profiles of RIS-EOP were evaluated compared with immediate release tablets in beagle dogs. The mean tmax and mean residence time of RIS-EOP for RIS and its active metabolite, 9-hydroxyrisperidone, were remarkably longer, compared with immediate release tablets. These results corroborated prolonged release of RIS from EOP formulations. Moreover, drug plasma levels with lower fluctuations could be achieved with RIS-EOP tablets. These results suggested that increasing drug solubility by adding or reacting with alkali/acid might be used for the preparation of EOP tablets of certain poorly water-soluble drugs.
研究了利培酮基本渗透泵（RIS-EOP）制剂的制备及其体外/体内评价。通过用柠檬酸调节利培酮的溶解度，开发了一种制备RIS-EOP片剂的方法。评估了渗透剂和半透膜组成对药物释放曲线的影响。通过正交设计优化了RIS-EOP的剂型。最佳剂型的体外释放曲线在长达12小时内实现了利培酮的近似零级释放。在比格犬中，将RIS-EOP的药代动力学曲线与速释片剂进行了比较。与速释片剂相比，RIS-EOP中利培酮及其活性代谢物9-羟基利培酮的平均达峰时间和平均驻留时间明显更长。这些结果证实了利培酮从EOP制剂中的缓释效果。此外，RIS-EOP片剂可实现较低波动的药物血浆水平。这些结果表明，通过与碱/酸添加或反应来提高药物溶解度，可用于制备某些水溶性差的药物的EOP片剂。
