Formulation Strategies for Ezetimibe and Its Combinations: Advancing Biopharmaceutical and Therapeutic Potential

Ezetimibe is a cholesterol absorption inhibitor widely used in the treatment of dyslipidemia. However, its clinical efficacy is limited by poor aqueous solubility and low oral bioavailability. Therapeutic guidelines on dyslipidemia recommend ezetimibe as an adjunct or alternative to statins, particularly in patients who are intolerant to high-dose statins or have inadequate LDL-C reduction. This review summarizes recent advances in ezetimibe formulations, including single-active and combination systems, and discusses their effects on solubility, pharmacokinetics, and therapeutic outcomes. The analysis is based on literature published within the last decade (2015-2025) from reputable scientific databases. Advanced strategies such as solid-state modification, particle size reduction, and lipid or surfactant-based delivery systems have significantly enhanced drug dissolution. In vivo studies report relative bioavailability improvements of approximately 120 to 800% compared to pure drug suspensions/marketed products, translating into favorable pharmacodynamic profiles. Beyond single-active systems, innovative co-delivery with statins such as simvastatin, atorvastatin, rosuvastatin, and lovastatin has demonstrated added pharmacological synergy and supports the development of fixed-dose combination products. Collectively, these advances provide strong evidence that optimized ezetimibe formulations in single-active or combination systems have strong potential to improve the biopharmaceutical profile and future therapeutic application in dyslipidemia management.