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 1–3 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.