Physicochemical and Pharmacokinetic Characterization of Amorphous Solid Dispersion of Meloxicam with Enhanced Dissolution Property and Storage Stability

Masanori Ochi, Keisuke Kimura, Atsushi Kanda, Takaki Kawachi, Akitoshi Matsuda, Kayo Yuminoki, Naofumi Hashimoto

The aim of the present study was to develop amorphous solid dispersion (ASD) of meloxicam (MEL) for providing rapid onset of action. ASDs of MEL with polyvinylpyrrolidone (PVP) K-30 (MEL/PVP), HPC-SSL (MEL/HPC), and Eudragit EPO (MEL/EPO) were prepared. The physicochemical properties were characterized by focusing on morphology, crystallinity, dissolution properties, stability, and the interaction of MEL with coexisting polymers. MEL/EPO was physicochemically stable after storage at 40°C/75% RH for 30 days. In contrast, recrystallization of MEL was observed in MEL/PVP and MEL/HPC at 40°C/50% RH for 30 days. Infrared spectroscopic studies and (1)H NMR analyses of MEL/EPO revealed that Eudragit EPO interacted with MEL and reduced intermolecular binding between MEL molecules. Intermolecular interaction of drug molecules is necessary for the formation of crystalline. Thus, the interaction of MEL with Eudragit EPO and interruption of the formation of supramolecular interaction between MEL molecules might lead to the inhibition of crystal growth of MEL. Of all the MEL solid dispersions prepared, MEL/EPO showed the largest improvement in dissolution behavior. Oral administration of MEL/EPO to rats showed rapid and enhanced MEL exposure with a 2.4-fold increase in bioavailability compared with crystalline MEL. Based on these findings, MEL/EPO was physicochemically stable and provided a rapid onset of action and enhanced bioavailability after oral administration.