A novel combination of Soluplus®/Poloxamer for Meloxicam solid dispersions via hot melt extrusion for rapid onset of action. Part 2: comparative bioavailability and IVIVC

Abstract

Objective Bioavailability of Meloxicam (MLX) from solid dispersions (SDs), against innovator product Mobic® in humans was conducted. Furthermore, to establish a good in vitro–in vivo correlation (IVIVC); dissolution studies were carried-out in different media. Methods MLX/SDs was prepared using Soluplus/Poloxamer via hot-melt-extrusion (EXT-SD) and fusion melt (FUS-SD) techniques. A single oral dose (15 mg), three periods, crossover study of MLX/SDs and Mobic® in four healthy humans under fed conditions was carried-out. In vitro dissolution was studied in pH 1.2, distilled water (pH 6.4), and biorelevant simulated gastric media in pre- and post-prandial states. Level A IVIVC was carried-out by comparing time-scaled fraction dissolved versus fraction absorbed and calculated using the Wagner-Nelson method. Multiple level C models were developed for C max and AUC0–96 versus % dissolved at different time-points. Internal predictability was evaluated for both IVIVC models. Results MLX rate of absorption (T max) from EXT-SD, FUS-SD, and Mobic® was 1.5, 3.0, and 4.0 h, respectively. Moreover, 1.45- and 1.40-folds increase in AUC0–∞ and C max, was obtained for EXT-SD versus Mobic®, respectively, while FUS-SD gave the lowest extent of drug absorption. EXT-SD provided highest dissolution profiles in all studied media. IVIVC models showed linear-regression (R 2≥0.90) and prediction errors (≤10%) in water and post-prandial simulated gastric media. Conclusion Hot-melt-extrusion technology promises an ideal alternative for enhancing MLX extent of absorption compared to Mobic® with T max value almost equal to the reported intramuscular injection. Predictive IVIVC was established for in vitro dissolution profile and in vivo performance.