A pilot human pharmacokinetic study and influence of formulation factors on orodispersible tablet incorporating meloxicam solid dispersion using factorial design

Abstract

Meloxicam (MLX) suffers from poor aqueous solubility leading to slow absorption following oral administration; hence, immediate release MLX tablet is unsuitable in the treatment of acute pain. This study aims to overcome such a drawback by increasing MLX solubility and dissolution using PEG solid dispersion (SD), then, to investigate the feasibility of incorporating the SD into orodispersible tablets (ODTs). A 2³ full factorial design was employed to investigate the influence of three formulation variables on MLX ODTs. The selected factors: camphor (X₁) as pore-forming material, and croscarmellose sodium (X₂) as superdisintegrant, showed significant positive influence, while PEG content (X₃) was proved to negatively affect both disintegration and wetting times. In addition, isomalt increased disintegration and wetting times when compared to mannitol as diluents. The pharmacokinetic assessment of the optimum ODT formulation in healthy human subjects proved that the faster MLX dissolution by using PEG solid dispersion at pH 6.8 resulted in more rapid absorption of MLX. The rate of absorption of MLX from ODT was significantly faster (p = 0.030) with a significantly higher peak plasma concentration (P = 0.037) when compared to the marketed immediate release MLX tablet with a mean oral disintegration time of 17 ± 3 s.

Keywords::

• Meloxicam
• solid dispersion
• mannitol
• isomalt
• orodispersible tablets
• pharmacokinetic