Pharmaceutical Cocrystals of Ribavirin with Reduced Release Rates

Cocrystals have been extensively utilized to improve drugs properties. Ribavirin is a water-soluble broad-spectrum antiviral drug and its application is severely limited by the peak-to-trough fluctuation in plasma drug concentrations and some undesirable side-effects. We show here that formation of cocrystals may be a useful approach to overcome this problem by reducing the release rate of ribavirin. Three cocrystals of ribavirin with 3,5-dihydroxybenzoic acid (1), gallic acid (2), and barbituric acid (3) were successfully prepared and characterized by powder and single crystal X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis, as well as dynamic vapor sorption measurement. The dissolution process revealed that 13 showed a reduced release rate as compared to ribavirin in the buffer solution representing intestinal pH 6.8. This study indicates that the release rate of ribavirin can be manipulated over a wide range by the formation of cocrystals, which may subsequently help lower its peak-to-trough fluctuation in plasma concentrations.