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.

Objective: Bioavailability of Meloxicam (MLX) from solid dispersions (SDs), against innovator product Mobic in humans was conducted. Furthermore, to establish a good - 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. 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 and AUC versus % dissolved at different time-points. Internal predictability was evaluated for both IVIVC models.

Results: MLX rate of absorption ( ) 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 AUC and , 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 ( ≥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 value almost equal to the reported intramuscular injection. Predictive IVIVC was established for dissolution profile and performance.