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

Abstract

Most drugs have low solubility in aqueous media, which influences drug efficacy and bioavailability. Many approaches have been developed to improve drug solubility. Recently, crystal engineering as a novel method was applied to adjust drug physicochemical properties such as solubility. Aim: The aim of this study is the preparation and characterization of piroxicam cocrystals and evaluation of aqueous solubility at different pHs and in presence of beta-cyclodextrin as a complexing agent.Method:Cocrystals of piroxicam with benzoic acid and saccharin were prepared by the slurry method. A certain molar ratio (1:1) of piroxicam and coformer were added to solvents, then the obtained 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 were determined in different media, including phosphate buffer solution at pH range 2-7 and β-cyclodextrin at different concentrations. Then, their effects on the solubility and stability of cocrystals were investigated.Results:The formation of cocrystals was confirmed by PXRD and DSC. Additive concentrations of beta-cyclodextrin increases the thermodynamic solubility of both cocrystals. Also, increasing the concentration of beta-cyclodextrin enhances solution stability of piroxicam-saccharin cocrystal, but it does not show a positive effect on solution stability of piroxicam-benzoic acid cocrystal. The thermodynamic solubility of both cocrystals improves with increasing pH of the solution. At different pHs, the solution stability of piroxicam-benzoic acid cocrystal is variable, however in the case of piroxicam-saccharin cocrystal a decrease in solution stability is observed.Conclusion:Beta-cyclodextrin has the ability to improve the thermodynamic solubility of both cocrystals and improves solution stability of piroxicam-saccharin cocrystal. In addition, the pH of the solution affects the thermodynamic solubility and solution stability of piroxicam cocrystals.