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

Abstract

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^®) 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^® (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.

Keywords:

• Meloxicam pellets
• hot melt extrusion
• rapid onset of action
• soluplus
• ^®
• long-term stability
• comparative bioavailbility

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.