Department of Pharmaceutics, China Pharmaceutical University, Nanjing, PR China.
Drug Deliv. 2011 Jul;18(5):361-6. doi: 10.3109/10717544.2011.557788. Epub 2011 Mar 23.
The aim of the present study was to design a depot delivery system of ropivacaine hydrochloride using multivesicular liposomes (RP-MVLs) to overcome the limitations of conventional therapies and to investigate it's in vivo effectiveness for sustained delivery. RP-MVLs were prepared by the multiple emulsion method. Appearance, particle size, encapsulation efficiency, zeta potential, and initial stability of RP-MVL were also studied. The in vitro release of RP-MVLs formulations was found to be in a sustained manner. Three batches of RP-MVLs were prepared and the release profile in vitro fitted to a first-order equation. RP-MVLs releasing mechanism was also studied and it was indicated that the drug released from MVLs by diffusion and erosion. Following subcutaneous administration to rats, the time to reach maximum (T(max)) of RP-MVLs formulations was significantly (p < 0.01) later than that of RH solution. The concentrations of RP-MVLs have steadily changed in the low level, which significantly (p < 0.01) lower than RH solution. T(1/2) and MRT were significantly prolonged (p < 0.01). Besides, AUC was also increased significantly (p < 0.01). The increase in AUC and decrease in C(max) reflects that the MVL formulations could reduce the toxic complications and limitations of conventional injected formation therapies.
本研究旨在设计盐酸罗哌卡因的储库型给药系统，采用多室脂质体（RP-MVLs）克服传统疗法的局限性，并研究其在体内的持续递送效果。RP-MVLs 通过复乳法制备。还研究了 RP-MVL 的外观、粒径、包封效率、Zeta 电位和初始稳定性。RP-MVLs 制剂的体外释放呈持续方式。制备了三批 RP-MVLs，体外释放曲线符合一级方程。还研究了 RP-MVLs 的释放机制，表明药物通过扩散和侵蚀从 MVLs 中释放。RP-MVLs 制剂经皮下给予大鼠后，T(max)明显（p < 0.01）晚于 RH 溶液。RP-MVLs 的浓度在低水平稳定变化，明显（p < 0.01）低于 RH 溶液。T(1/2)和 MRT 明显延长（p < 0.01）。此外，AUC 也明显增加（p < 0.01）。AUC 的增加和 C(max)的降低反映了 MVL 制剂可以减少传统注射制剂疗法的毒性并发症和局限性。
