The effect of pH and beta-cyclodextrin on solubility and solution stability of piroxicam cocrystals

Most drugs have low solubility in aqueous media, which influences drug efficacy and bioavailability. Various approaches have been developed to improve drug solubility. Crystal engineering has recently emerged as a novel method to modify drug physicochemical properties, such as solubility. The objective of this study is to prepare and characterize piroxicam cocrystals, as well as to assess their aqueous solubility in different pH conditions and in the presence of β-cyclodextrin (βCD) as a complexing agent. Cocrystals of piroxicam with benzoic acid and saccharin were generated using the slurry method. A certain molar ratio (1:1) of piroxicam and coformer was mixed in solvent, then the resulting suspension was left at room temperature. The prepared cocrystals were characterized by powder X-ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC). The thermodynamic solubility of piroxicam, coformers, and cocrystals was determined in different media, including phosphate buffer solution at pH levels ranging from 2 to 7, and βCD at various concentrations. Then, the impact of these factors on the solubility and solution stability of the cocrystals was investigated. The addition of βCD at different concentrations affects the thermodynamic solubility of both cocrystals. Furthermore, increasing the concentration of βCD enhances the solution stability of the piroxicam-saccharin cocrystal, but it does not show a positive effect on the solution stability of the piroxicam-benzoic acid cocrystal. The thermodynamic solubility of both cocrystals improves with higher pH levels of the solution. At different pH levels, the solution stability of the piroxicam-benzoic acid cocrystal is variable, however, in the case of piroxicam-saccharin cocrystal a decrease in solution stability is observed. Overall, βCD and the final pH of the solution significantly influence the thermodynamic solubility and solution stability of the studied cocrystals. © 2025 Elsevier B.V.