Lu Yaxin, Yu Yeling, Tang Xing
School of Pharmacy 32 mail box, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, Liaoning Province, PR China.
J Pharm Sci. 2007 Dec;96(12):3252-62. doi: 10.1002/jps.21091.
The objective of this study was to develop sustained-release sucrose acetate isobutyrate (SAIB) in situ formulations of risperidone for parenteral delivery. The formulations contained SAIB, solvent (anhydrous ethanol, ethyl lactate, or N-methyl-2-pyrrolidone), and additives such as polylactic acid (PLA). In vitro release profiles of risperidone from the SAIB formulations, which followed the Higuchii square root law, were obtained. An increase in SAIB content from 75% to 85% resulted in a reduction in the initial burst and the rate of risperidone release. The initial drug release could be increased by reducing the pH of the release medium and the release rate could be increased by an increase in drug loading. The burst release fell significantly from 20.0% to 3.5% following the inclusion of 10% (w/w) PLA in the formulations. In the case of this high viscosity depot system containing SAIB, anhydrous ethanol, PLA, and 25 mg/g risperidone, the in vivo biocompatible test results obtained support the use of SAIB as an injectable risperidone sustained-release formulation.
本研究的目的是开发用于肠胃外给药的利培酮醋酸异丁酸蔗糖酯(SAIB)原位制剂。这些制剂包含SAIB、溶剂(无水乙醇、乳酸乙酯或N-甲基-2-吡咯烷酮)以及聚乳酸(PLA)等添加剂。获得了利培酮从SAIB制剂中的体外释放曲线,其遵循 Higuchii 平方根定律。SAIB 含量从 75%增加到 85%导致初始突释和利培酮释放速率降低。通过降低释放介质的 pH 值可增加初始药物释放,通过增加药物载量可提高释放速率。制剂中加入 10%(w/w)PLA 后,突释从 20.0%显著降至 3.5%。对于这种含有 SAIB、无水乙醇、PLA 和 25 mg/g 利培酮的高粘度长效注射系统,所获得的体内生物相容性测试结果支持将 SAIB 用作可注射的利培酮缓释制剂。