Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability

The major goal of this research work was to augment bioavailability of the fixed-dose combination drugs, ledipasvir (LDV) and sofosbuvir (SBV) by developing orodispersible tablets and films and to estimate it by in vivo pharmacokinetic studies in rats. The pre-optimized amorphous solid dispersions of the LDV-SBV combination with HPMC E15 were made into orodispersible films (ODFs) and the pre-optimized inclusion complexes with dimethyl-beta-cyclodextrin were made into orodispersible tablets (ODTs). The ODFs and ODTs were studied for the in vitro physical characterization studies and dissolution. Best of both the products were evaluated for in vivo pharmacokinetic studies in comparison with the marketed formulation of film coated tablets, Ledifos. The dissolution rate constants for the LDV from the optimized ODFs, ODTs and the marketed tablets were found to be 0.269, 0.13 and 0.073 min.-1 respectively. The dissolution rate constants for the SBV from the optimized ODFs, ODTs and the marketed tablets were found to be 0.302, 0.168 and 0.094 min.-1 respectively. Area under the curve (AUC) values for the LDV from the films, tablets and the marketed tablets were found to be 4231.4, 4050.3 and 3662.5 h*ng/mL respectively. AUC values for the SBV from the films, tablets and the marketed tablets were found to be 2173.2, 2084.6 and 1452.4 h*ng/mL respectively. Conclusion: The obtained results indicated that the optimized ODFs and the ODTs exhibited improved in vitro dissolution and in vivo bioavailability for the fixed-dose combination of LDV and SBV over the reference product.