Multivesicular liposome formulations for the sustained delivery of ropivacaine hydrochloride: Preparation, characterization, and pharmacokinetics

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.