Drug-drug cocrystals of theophylline with quercetin

Drug-drug cocrystals have received growing attention in pharmaceutical industry for the ability to present a strategy for the development of fixed-dose combination drugs. In this study, two novel drug-drug cocrystals (one hydrate and one anhydrate) composed of theophylline (THP) and quercetin (QUE) were obtained. The hydrate, THP-QUE-H, was prepared by liquid-assisted grinding method, and the anhydrate, THP-QUE-A, was harvested by heat-treatment of the THP-QUE-H at about 235 °C. Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis showed that the THP-QUE-H transformed to the THP-QUE-A at about 235 °C and the melting point was 247 °C, indicating both the cocrystals were thermally stable at environment temperature. Additionally, both cocrystals maintained a stable state after 30-day under 25 °C/90% RH condition or after 30-day under 25 °C/15% RH condition. Such results indicate the two THP-QUE cocrystals might show potential as suitable solid forms for the further development as pharmaceutical products. [Display omitted] 1.Two novel drug-drug cocrystals composed of theophylline (THP) and quercetin (QUE) were obtained.2.One hydrate (THP-QUE-H) and one anhydrate (THP-QUE-A) were prepared.3.THP-QUE-H could transform to THP-QUE-A after heating at about 235 °C.4.Both cocrystals were found to exhibit higher solubility for QUE.5.Thermo properties and humidity stability were investigated.