Study on optimization of ternary complex of piroxicam-β-cyclodextrin-lysine inclusion in supercritical CO2

Abstract

A variety of pharmaceutical agents including piroxicam (PC), a non-steroidal anti-inflammatory drug, have inaccessible bioavailability and dissolution. Piroxicam is a bioactive compound classified as a non-steroidal anti-inflammatory drug (NSAID). However, its low solubility in water imposes a serious limitation for its application in the pharmaceutical industry. Using cyclodextrins to form complexes can enhance the dissolution rate, solubility, and bioavailability of piroxicam. In this study, piroxicam/β-cyclodextrin complexes are prepared in supercritical carbon dioxide (SC-CO₂) in the solid state and the process was optimized using response surface methodology (RSM). UV-Vis spectroscopy, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and dissolution profile in water were used to characterized the complex under optimized temperature, residence time, moisture, and ternary agent. Finally, the maximum reaction yield of the inclusion complex was predicted to be 95% at the optimal conditions of 266 bar, 136^oC, 1.84:1 ratio of cyclodextrin:piroxicam, and 1.5:1 ratio of lysine:piroxicam. Large scale production of inclusion complexes can be developed from the results of this work on optimizing conditions.