Solid Self Nanoemulsifying Drug Delivery System as carrier for the enhancement of bioavailability of Benidipine with Telmisartan

Abstract

Background: Benidipine (BD) and Telmisartan (TEL), co-administered antihypertensive medicines in the BCS class II group, are characterized by inadequate bioavailability due to restricted water solubility. Self-nano emulsifying drug delivery systems (SNEDDS) offer efficient solubilization for weakly water-soluble medicines due to their ternary ingredients' solubilization and nanonization activity, driven by surfactant and cosolvent. SNEDDS formulations comprise surfactants and cosolvents that facilitate nano droplet dispersion. Objective: This study seeks to investigate the antihypertensive activity of solidified selfnanoemulsifying drug delivery systems (S-SNEDDS) comprising BD and TEL. Methods: Hypertension was produced in rats with oral 10% glucose treatment for three weeks. Animals were grouped: Group 1 as Normal control, Group 2 as Hypertensive control, Group 3 as Hypertensive treated with S-SNEDDS formulation of BD with TEL, and Group 4 as Hypertensive treated with conventional BD-TEL suspension. Rats with a mean blood pressure ≥150 mm Hg were selected. After baseline blood pressure measurement, Group 3 and 4 animals received oral doses of 4 mg BD and 40 mg TEL/kg from optimized S-SNEDDS and pure drug, respectively. Blood pressure was non-invasively monitored using a tail-cuff sensor and Biopack MP36 data gathering system at intervals of 0, 2, 6, 12, and 24 hours. Results and Discussion: In contrast to the hypertensive control group, S-SNEDDS treatment contributed to a progressive blood pressure reduction, peaking at 45 minutes and persisting for 75 minutes. This reduction was statistically different from the control group, demonstrating superior hypertension control compared to BD-TEL suspension. The improved water solubility of BD and TEL due to surfactant presence, together with fast globule dispersion, absolutely contributes to the observed antihypertensive benefits of the SNEDDS formulation.