Mixed Pluronic/lecithin micelles formulation for oral bioavailability of candesartan cilexetil drug: In-vitro characterization and In-vivo pharmacokinetic investigations.

OBJECTIVE: This study aimed to develop a mixed polymeric micelle formulation incorporating candesartan cilexetil (CAND) drug to enhance its oral bioavailability for the better treatment of hypertension.

METHODS: A Box-Behnken design was utilized to optimize the CAND-incorporated mixed polymeric micelles formulation (CAND-PFLC) consisting of Pluronics (P123 and F68) and lecithin (LC). The optimized CAND-PFLC micelles formulation was characterized for size, shape, zeta potential, polydispersity index (PDI), and entrapment efficiency (%EE). An in-vitro release study, ex-vivo permeability investigation, and an in-vivo pharmacokinetic analysis were carried out to evaluate the performance of the formulation.

RESULTS: The optimized CAND-PFLC micelles formulation demonstrated a spherical shape, a particle size of 44 ± 2.03 nm, a zeta potential of -7.07 ± 1.39 mV, a PDI of 0.326 ± 0.06, and an entrapment efficiency of 87 ± 3.12%. The formulation exhibited excellent compatibility, better stability, and a non-crystalline nature. An in-vitro release study revealed a faster drug release of 7.98% at gastric pH in 2 hrs and 94.45% at intestinal pH within 24 hrs. The ex-vivo investigation demonstrated a significantly enhanced permeability of CAND, with 94.86% in the micelle formulation compared to 9.03% of the pure drug. In-vivo pharmacokinetic analysis showed a 4.11-fold increase in oral bioavailability of CAND compared to the marketed formulation.

CONCLUSION: The CAND-PFLC mixed micelle formulation demonstrated improved performance compared to pure CAND, indicating its potential as a promising oral drug delivery system for the effective treatment of hypertension.