摘要
目的研究外消旋体酮洛芬（rac—Ket）在酸性释放介质中的立体选择性释放行为。方法以专属性的手性HPLC考察酮洛芬可注射植入剂在pH2．5释放介质中的对映体选择性释放行为。结果体外释放实验结果表明，以可生物降解的乳酸-乙醇酸共聚物（D，L—PLG）为载体制成的外消旋体酮洛芬可注射植入剂，在pH2．5的酸性释放介质中可维持约2．5月的缓慢释放。从立体选择性的角度观察，S-（＋）-Ket的释放略快于尺-（-）．Ket，S／R—Ket的比值在1．01～1．03之间，但经独立样本的t检验，认为这种差异没有显著性（P〉0．05）。这与我们过去以pH7．4为介质的对映体释放结果不同，显示载体D，L—PLG在不同pH条件下的降解方式可能影响对映体的释放行为。结论与在pH7．4释放介质中的研究结果不同，7％rac—Ket可注射植入剂在酸性条件下（pH2．5）的对映体释放缺少选择性。
OBJECTIVE To investigate the stereoselective release from racemic ketoprofen injectable implants in pH 2.5 release medium. METHODS The enantioselective release at pH 2. 5 was evaluated by a reversed-phase HPLC analytical method. S-（ ＋ ） and R-（ - ） enantiomers of ketoprofen were determined simultaneously in release samples. RESULTS In vitro release study showed that racemic ketoprofen implants obtained sustained release of the drug lasting about 2. 5 months in a pH 2. 5 release medium. Moreover, S-（ ＋ ）-Ket released faster than R-（ - ）-Ket in the implants containing 7% of rac-Ket and the ratio of S- to R-enantiomer ranged from 1. 01 to 1.03. However, there was no significant difference between two enantiomers. CONCLUSION Difference of stereoselective release between the acidic and the neutral release medium maybe relate to the various biodegradable PLG. Compared with the significant release difference between two enantiomers in vitro at pH 7.4, the release of two enantiomers from rac-Ket injectable implants at pH 2. 5 showed no stereoselectivity.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第3期199-202,共4页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(30772610)
浙江省自然科学基金资助项目(X205001)
浙江省科技厅资助项目(2006F13029)
浙江省卫生高层次创新人才培养工程项目(2008)
