Fabrication of Nanosuspension Directly Loaded Fast-Dissolving Films for Enhanced Oral Bioavailability of Olmesartan Medoxomil: In Vitro Characterization and Pharmacokinetic Evaluation in Healthy Human Volunteers

Olmesartan medoxomil (OM) is an antihypertensive drug with poor water solubility and low oral bioavailability (28.6%). Accordingly, this study aimed to formulate and evaluate OM nanosuspension incorporated into oral fast-dissolving films (FDFs) for bioavailability enhancement. OM nanosuspension was prepared by antisolvent-precipitation-ultrasonication method and characterized regarding particle size (122.67 +/- 5.03 nm), span value (1.40 +/- 0.51), and zeta potential (- 46.56 +/- 1.20 mV). Transmission electron microscopy (TEM) of the nanosuspension showed spherical non-aggregating nanoparticles. The nanosuspension was then directly loaded into FDFs by solvent casting technique. A full factorial design (2(2) x 3(1)) was implemented for optimization of the FDFs using Design-ExpertA (R) software. Physical and mechanical characteristics in addition to dissolution profiles of the FDFs were investigated. The optimum formula (FDF1) showed 0.43 +/- 0.02 kg/mm(2) tensile strength, 20.50 +/- 2.12 s disintegration time, and 87.53 +/- 2.50 and 95.99 +/- 0.25% OM dissolved after 6 and 10 min, respectively. Accelerated and long-term shelf stability studies confirmed the stability of FDF1. More than 75% OM was dissolved within 10 min from FDF1 compared with 9.80 and 47.80% for films prepared using coarse drug powder and market tablet, respectively. Relative bioavailability of FDF1 compared to market tablet was assessed in healthy human volunteers. The C-max value increased significantly from 66.62 +/- 14.95 to 179.28 +/- 23.96 ng/mL for market tablet and FDF1, respectively. Similarly, the AUC(0-72) value significantly increased from 498.36 +/- 217.46 to 1083.67 +/- 246.32 ng h/mL for market tablet and FDF1, respectively. Relative bioavailability of FDF1 was 209.28%. The highlighted results verified the effectiveness of OM nanosuspension-loaded FDFs in improving OM bioavailability.