Mechanistic Insights into Amorphous Solid Dispersions: Bridging Theory and Practice in Drug Delivery

Abstract

Improving the bioavailability of poorly water-soluble drugs presents a significant challenge in pharmaceutical development. Amorphous solid dispersions (ASDs) have garnered substantial attention for their capability to augment the solubility and dissolution rate of poorly water-soluble drugs, thereby markedly enhancing their bioavailability. ASDs, characterized by a metastable equilibrium where the active pharmaceutical ingredient (API) is molecularly dispersed, offer enhanced absorption compared to crystalline forms. This review explores recent research advancements in ASD, emphasizing dissolution mechanisms, phase separation phenomena, and the importance of drug loading and congruency limits on ASD performance. Principal occurrences such as liquid-liquid phase separation (LLPS) and supersaturation are discussed, highlighting their impact on drug solubility, absorption and subsequent bioavailability. Additionally, it addresses the role of polymers in controlling supersaturation, stabilizing drug-rich nanodroplets, and inhibiting recrystallization. Recent advancements and emerging technologies offer new avenues for ASD characterization and production and demonstrate the potential of ASDs to enhance bioavailability and reduce variability, making possible for more effective and patient-friendly pharmaceutical formulations. Future research directions are proposed, focusing on advanced computational models for predicting ASD stability, use of novel polymeric carriers, and methods for successful preparations.

Keywords: Amorphous solid dispersions (ASDs); Dissolution mechanisms; Enhanced bioavailability; Liquid–liquid phase separation (LLPS); Role of polymers.