Amorphous Solid Dispersions for BCS Class II Antihyperlipidemic Drugs: From Drug-Polymer Interactions to in vivo...

Hyperlipidemia is a major health concern worldwide, and oral therapies like statins, fibrates, and ezetimibe are severely limited by their poor water solubility, classified in the Biopharmaceutics Classification System (BCS) Class II. Although amorphous solid dispersion (ASD) technology shows promise in overcoming these biopharmaceutical limitations, a comprehensive synthesis linking molecular drug-polymer interactions to dissolution enhancement, pharmacokinetic performance, and preclinical in vivo efficacy remains underreported. Addressing this gap, this review comprehensively evaluates BCS Class II antihyperlipidemic ASD frameworks. A comprehensive literature search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar for studies published between 2015 and 2025 (n=16). ASD conversion significantly enhances dissolution kinetics via the "spring and parachute" mechanism. Specific molecular interactions, including hydrogen bonding and hydrophobic interactions with polymeric carriers, restrict molecular mobility and effectively inhibit recrystallization. Biopharmaceutical studies confirmed that these molecular pathways translate into improved systemic exposure in rodent dyslipidemia models, with significant increases in peak plasma concentration (C_max ) and area under the curve (AUC). In addition, preclinical pharmacodynamic studies typically show increased lipid-lowering efficacy, with significant reductions in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) compared with pure crystalline medicines. Overall, although ASD formulations dramatically improve in vitro dissolution, pharmacokinetic characteristics, and preclinical performance, their clinical translational impact still needs full validation. Therefore, future studies should focus on human head-to-head clinical trials, long-term physical stability studies, and scalable manufacturing to enable the commercial translation of antihyperlipidemic ASDs.