Preparation, characterization and in-Vitro/in-Vivo evaluation of meloxicam extruded pellets with enhanced bioavailability and stability

Objective The present study involved enhancement of Meloxicam (MX) oral absorption for rapid onset of therapeutic action. A challenging approach using hot-melt-extrusion technique (HME) for production of stable novel preparation of MX pellets was successfully proposed. Methods Manipulating HME processing parameters (barrel-temperatures and screw-speed) and proper polymer(s) selection (Soluplus, a combination of Soluplus/Poloxamar and Polyethylene Glycol 6000) were the main strategies involved for productive extrusion of MX. Evaluation of MX solid-state (TGA, DSC and PLM), absolute percent crystallinity, in-vitro dissolution (in acidic/aqueous pHs), and stability testing in accelerated conditions up to 6-months as well as a long-term shelf for 36-months were performed. A comparative bioavailability study of selected MX-Pellets was carried-out against the innovator product (Mobic(R)) in 6 healthy volunteers under fed-conditions. Results TGA, DSC and PLM analyses proved the dispersion of MX in amorphous-state within polymeric matrix by HME. MX/Soluplus pellets exhibited the lowest crystallinity % and best dissolution performance among other polymers in both pHs. In addition, presence of Soluplus safeguards final pellets stability under different storage conditions. MX rate of absorption (T-max) from Soluplus-based pellets attained a value of 45 min, which was 6-times faster than Mobic(R) (4.5 hr). Conclusion A promising oral MX formula prepared by HME was successfully developed with a rapid onset of analgesic action (T-max of 45 mins; almost 2-times faster than reported intramuscular injection), hence appropriate in the early relief of pain associated with rheumatoid arthritis and osteoarthritis. Moreover, the proposed formula was physico-chemically stable up to 36 months of shelf-life storage.

Automated summary

The present study successfully enhanced the oral absorption of Meloxicam (MX) for rapid therapeutic action by using the hot-melt-extrusion technique. The novel MX pellets showed improved stability, dissolution performance, and faster absorption rate compared to the innovator product Mobic(R). The Soluplus-based MX pellets achieved a T-max value of 45 minutes, which was 6 times faster than Mobic(R).