Self-microemulsifying Drug Delivery System for Solubility and Bioavailability Enhancement of Eprosartan Mesylate: Preparation, In-vitro , and In-vivo Evaluation

摘要

Background: Formulations of eprosartan mesylate with a surfactant, like Kolliphor HS 15, an oil phase like Labrafil M 1944 CS, and a cosurfactant Transcutol HP by employing a liquid self-microemulsifying drug delivery system (SMEDDS) after screening several vehicles have been studied. Objective: This study aimed to prepare a liquid self-microemulsifying drug delivery system for increasing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate. Methods: The micro-emulsion unit, achieved through the phase diagram and augmented with the central-composite design (CCD) surface response process, was adjusted into SMEDDS by lyophilization using sucrose as a cryoprotective agent. Particle size, self-emulsification time, polydispersion index (PDI), zeta potential, differential scanning calorimeter (DSC) screening, in-vitro drug release, and in-vivo pharmacokinetics were the essential features of the formulations. The subsequent DSC experimentation indicated that the drug was integrated into S-SMEDDS. Eprosartan mesylate loaded SMEDDS formulation showed greater in-vitro and in-vivo drug release than conventional solid doses. Results: SMEDDS has reported effectiveness in reducing the impact of pH of eprosartan mesylate, thereby improving its release efficiency. The HPLC method was successfully implemented to assess eprosartan mesylate concentration in Wister rat plasma after oral administration of commercial tablet EM, SMEDDS, and eprosartan mesylate. The pharmacokinetics parameters for rats were C max 1064.91 ± 225 and 1856.22 ± 749 ngmL -1 , T max 1.9 ± 0.3 hr, and 1.2 ± 0.4 hr and AUC 0~t were 5314.36 ± 322.61 and 7760.09 ± 249 ng/ml hr for marketed tablets and prepared SSMEDDS, respectively. When determined by AUC 0~1 , the relative bioavailability of eprosartan mesylate S-SMEDDC was 152.09 ± 14.33%. Conclusion: The present study reports the formulation of a self-microemulsifying drug delivery system for enhancing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate in an appropriate solid dosage form.