Design Development And Optimization of Nanoemulsion Formulation of Anti Hypertensive Drug

Abstract

The present research attempted to design and develop a nanoemulsion formulation of azilsartan medoxomil (AZL) to improve its aqueous solubility and oral bioavailability. Based on solubility profile ethyl oleate, tween 80, and transcutol P were selected as oil phase, surfactant, and co- surfactant respectively. Central composite design (CCD) suggested an optimized azilsartan medoxomil-nanoemulsion formulation (optimized AZL-NE formulation) having 1.25% oil, 15.73% Smix, and 90 seconds ultrasonication time which was found to have droplet size, percentage transmittance, and % cumulative drug release (%CDR) of 71.5 nm, 93.46 ± 1.13% and 90.14 ± 0.94% respectively. Furthermore, it exhibited 0.141 polydispersity index, 34.05 mV zeta potential, 1.413 ± 0.03 refractive index, 6.68 ± 0.22 pH, 28.17±0.52 cps viscosity and 96.98 ± 0.94% percentage drug content. Transmission electron microscopy (TEM) assessed the spherical shape with nanosize. Fourier Transform Infrared spectroscopy (FTIR) revealed the absence of any interaction between the drug and excipients. The % CDR was 1.71 times and % cumulative drug permeation was 2.1 times higher for optimized AZL-NE formulation than drug suspension through an intestinal segment of the rat which was also supported by confocal laser scanning microscopy (CLSM) studies. Optimized AZL-NE formulation provided 1.98 fold improved relative bioavailability than drug suspension. The Cmax and Tmax for optimized AZL-NE formulation were 1762.84 ng/mL and 2.50 h respectively whilst these were 1009.98 ng/mL and 3.20 h for drug suspension. The results of thermodynamic stability studies and storage stability studies revealed the stability of optimized AZL-NE formulation. Thus nanoemulsion formulation ensured the improved aqueous solubility and oral bioavailability of AZL. newline