Development of Immediate-Release Solid Dispersion Tablets of Bempedoic Acid with Enhanced Dissolution Performance and Stability

Abstract

Bempedoic acid, a recently introduced ATP-citrate lyase inhibitor, exhibits poor aqueous solubility, limiting its dissolution rate and oral bioavailability. The present study investigates the development of a poloxamer-based solid dispersion system, focusing on improving dissolution performance and elucidating the underlying physicochemical transformations.
Solid dispersions were prepared using Poloxamer 188 and polyethylene glycol (PEG 6000) via the kneading method at varying drug-to-polymer ratios. Preformulation and solid-state characterization, including FT-IR and differential scanning calorimetry, confirmed drug integrity and suggested partial modulation of crystallinity in the optimized system. Among the prepared formulations, the 1:1 drug–polymer ratio exhibited the highest solubility enhancement, achieving approximately a 20-fold increase compared to the pure drug.
The optimized solid dispersion was further formulated into immediate-release tablets and evaluated for micromeritic, mechanical, and performance characteristics. The tablets demonstrated acceptable hardness, low friability, rapid disintegration, and significantly reduced wetting time. In vitro dissolution studies revealed rapid drug release, with approximately 96% release achieved within 10 minutes, indicating a marked improvement over the untreated drug.
The enhanced dissolution behavior is attributed to improved wettability, reduced particle size, and possible partial amorphization induced by the hydrophilic carrier system. Stability studies confirmed the robustness of the formulation with no significant changes in drug content or release profile.