Development of Self-Microemulsifying Drug Delivery System to Improve Nisoldipine Bioavailability: Cell Line and In Vivo Evaluations : Development of Self-Microemulsifying Drug Delivery System

Abstract

The authors attempted to fabricate a novel lipid-based formulation of a lipophilic drug, nisoldipine (NISO). As NISO belongs to BCS class 2 drug, it suffers from low bioavailability (5%). Hence, the research was intended to ameliorate oral bioavailability of NISO via intestinal lymphatic transport. The NISO loaded self microemulsifying drug delivery system (SMEDDS) (NISO SMEDDS) was prepared using Peceol, Cremophor EL, and Transcutol HP. The Cremophor EL and Transcutol HP at 1:1 ratio showed maximum microemulsifying area, and average globule size was 16.78 ± 0.97 nm with PDI 0.121 ± 0.024. Cellular uptake studies (confocal microscopy and flow cytometry) using Caco-2 cells depicted higher fluorescence with coumarin-6 loaded SMEDDS as that of coumarin-6 solution which indicated deeper penetration. Mean fluorescence intensity (MFI) of coumarin-6 loaded SMEDDS was significantly improved (9.92-fold) in contrast to coumarin-6 solution. The NISO SMEDDS showed enhanced permeability (5.02 times) across Caco-2 cells compared to NISO suspension. The bioavailability improvement with NISO SMEEDS was 2.14 times relative to suspension, and lymphatic uptake was involved in oral absorption of NISO SMEDDS.

Keywords: Caco-2 cell line; bioavailability; lymphatic uptake; nisoldipine; self-microemulsifying drug delivery system.