Effects of Additives on the Physical Stability and Dissolution of Polymeric Amorphous Solid Dispersions: a Review.

Abstract

Polymeric amorphous solid dispersion (ASD) is a popular approach for enhancing the solubility of poorly water-soluble drugs. However, achieving both physical stability and dissolution performance in an ASD prepared with a single polymer can be challenging. Therefore, a secondary excipient can be added. In this paper, we review three classes of additives that can be added internally to ASDs: (i) a second polymer, to form a ternary drug-polymer-polymer ASD, (ii) counterions, to facilitate in situ salt formation, and (iii) surfactants. In an ASD prepared with a combination of polymers, each polymer exerts a unique function, such as a stabilizer in the solid state and a crystallization inhibitor during dissolution. In situ salt formation in ASD usually leads to substantial increases inthe glass transition temperature, contributing to improved physical stability. Surfactants can enhance the wettability of ASD particles, thereby promoting rapid drug release. However, their potential adverse effects on physical stability and dissolution, resulting from enhanced molecular mobility and competitive molecular interaction with the polymer, respectively, warrant careful consideration. Finally, we discuss the impact of magnesium stearate and inorganic salts, excipients added externally upon downstream processing, on the solid-state stability as well as the dissolution of ASD tablets.