Hydroxypropyl methylcellulose acetate succinate as an exceptional polymer for amorphous solid dispersion formulations: A review from bench to clinic

[Display omitted] Amorphous solid dispersions (ASDs) are a proven system for achieving a supersaturated state of drug, in which the concentration of drug is greater than its crystalline solubility. The usage of Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS) in the development of ASDs has grown significantly, as evidenced by the fact that majority of commercially approved ASD formulations are based on HPMCAS. HPMCAS has been widely utilized as a solubility enhancer and precipitation inhibitor or stabilizer to achieve supersaturation and inhibit crystallization of drugs in the gastrointestinal tract. The characteristics of HPMCAS ASDs such as less hygroscopic, strong drug-polymer hydrophobic interactions, high solubilization efficiency, greater potential to generate, maintain drug supersaturation and crystallization inhibition outperform other polymeric carriers in ASD development. Furthermore, combining HPMCAS with other polymers or surfactants as ternary ASDs could be a viable approach for enhancing oral absorption of poorly soluble drugs. This review discusses the concepts of supersaturation maintenance or precipitation inhibition of HPMCAS in the ASD formulations. In addition, the mechanisms underlying for improved dissolution performance, oral bioavailability and stability of HPMCAS ASDs are explored.