Multicomponent Crystal Formation of Dexibuprofen-Caffeine to Improve Solubility

Abstract

Alteration of solid form via a multicomponent crystal formation can be a choice to improve the solubility of a poor  solubility drug, such as dexibuprofen. The purpose of this research was to produce dexibuprofen-caffeine (DXI-CAF)  multicomponent crystal and to evaluate its solubility and dissolution rate. Preliminary investigation to predict the  multicomponent crystal formation was conducted by observing crystal morphology by polarization microscope and  knowing phase solubility type of DXI in caffeine solution. Liquid-assisted grinding (LAG) method was used to produce  DXI-CAF multicomponent crystal and ethanol was used to accelerate its formation. Powder X-ray diffractometer (PXRD)  and differential scanning calorimeter (DSC) were utilized to analyze DXI-CAF multicomponent crystal formation.  Evaluation of physicochemical properties was carried out by the solubility testing in water and pH 1.2, 4.5, and 6.8. The dissolution rate tests were also performed in the same pH. The DXI-CAF showed a different crystal morphology from  pure DXI and CAF after crystallized in ethanol. Meanwhile, a BS type curve was obtained from the determination of  phase solubility. The LAG product revealed a distinctive PXRD pattern and DSC thermogram that was different from pure  DXI and CAF, thereby indicating DXI-CAF multicomponent crystal formation. The increase in solubility and dissolution rate was shown in the DXI-CAF multicomponent crystal in all pH. Succinctly, DXICAF multicomponent crystal  can be prepared by the LAG method which shows the potential in enhancing solubility and dissolution rate of  dexibuprofen.