Solid dispersions of bedaquiline fumarate to improve its pharmaceutical attributes: A comparative study between PEG and PVP

Abstract

ObjectivesThe therapeutic delivery of hydrophobic drugs via solid dispersion is an appealing methodology to enhance the dissolution rate and ultimately the in vivo bioavailability. The objective of current investigation was to enhance the solubility of anti-tubercular drug bedaquiline fumarate (BQF) via solid dispersion strategy, where the influence of polyethylene glycol and polyvinylpyrrolidone on the performance of solid dispersions was determined. MethodsBQF-solid dispersions with polyethylene glycol and polyvinylpyrrolidone were fabricated via solvent evaporation technique and evaluated for solubility, in vitro dissolution studies, cytotoxicity, cellular uptake, intestinal permeability, and pharmacokinetics. ResultsSolubility of BQF was improved by 6.4-fold and 13.44-fold with polyethylene glycol and polyvinylpyrrolidone-based ternary solid dispersions, respectively. The in vitro dissolution studies revealed significant enhancement in dissolution rate of BQF. The in vivo pharmacokinetic results demonstrated that solid dispersions significantly improved the pharmacokinetic parameters of BQF. The relative bioavailability of BQF with polyvinylpyrrolidone-based ternary solid dispersion was found to be enhanced by 173% and 154%, under fasted and fed state, respectively, when compared to BQF suspension. ConclusionsOur study reaffirms the applicability of solid dispersions as an alternative formulation strategy to improve the biopharmaceutical attributes of BQF in tuberculosis therapy.