Co-crystallization of sofosbuvir with sugars for enhanced dissolution rate

Abstract

Sofosbuvir is one of the direct acting antiviral agents which is approved in the treatment of chronic HCV in combination with other agents. The low aqueous solubility of sofosbuvir resulted in slow dissolution which is supposed to be responsible for its low and variable bioavailability after oral administration. Accordingly, the objective of this work was to investigate the effect of co-crystallization of sofosbuvir with hydrophilic sugars on its crystalline structure and dissolution rate. Mixtures of sofosbuvir with hydrophilic sugars at various molar ratios were prepared by ethanol assisted kneading followed by drying. The dry products were then characterized by attenuated total reflectance fourier transform infrared spectroscopy (ATR FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and in vitro dissolution studies. Combined instrumental analysis reflected development of new crystalline species of co-crystal type. This was evidenced by the existence of hydrogen bonding as shown from FTIR spectra, change in the thermal behaviour and appearance of new diffraction peaks in the diffractograms recorded by XRD. The co-crystallization was associated by weakening of intermolecular bonds which resulted in significant increase in the dissolution rate of sofosbuvir. The study introduced hydrophilic sugars as co-crystal co-formers for enhanced dissolution of sofosbuvir.