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

Objectives

The 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.

Methods

BQF-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.

Results

Solubility 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.

Conclusions

Our study reaffirms the applicability of solid dispersions as an alternative formulation strategy to improve the biopharmaceutical attributes of BQF in tuberculosis therapy.

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Materials

BQF was acquired from Clearsynth India Pvt. Ltd. (India). PVP K-30 and PEG 8000 were obtained from Sigma-Aldrich (St. Louis, USA). Ammonium acetate and polyvinylidene difluoride syringe filter (PVDF) was obtained from Himedia (Thane West, India). The analytical and high-performance liquid chromatography (HPLC) grade methanol and acetic acid were obtained from Merck Ltd. (Mumbai, India).

Vishwas P. Pardhi, Anchal Pathak, Keerti Jain, Solid dispersions of bedaquiline fumarate to improve its pharmaceutical attributes: A comparative study between PEG and PVP, Journal of Drug Delivery Science and Technology, 2024, 105461, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.105461.