<p dir="ltr">Amorphous solid dispersions (ASDs) are being widely used as enabling formulations for poorly water soluble drugs. An ASD is a molecular level mixture of an amorphous drug and a polymer to form a single-phase homogeneous blend. The amorphous form of a drug provides a higher transient solubility compared to equilibrium crystalline solubility, whereby the presence of a polymer of appropriate properties aids in crystallization inhibition. Polymers also improve the release rate of the drug from the ASD relative to the release rate of neat amorphous drug, specifically for release regimens where both drug and polymer release congruently. Hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based ASDs tend to show congruent release of drug and polymer across multiple drug loadings, providing a significant dissolution improvement even beyond the amorphous solubility of a drug. Enteric polymers such as HPMCAS have been studied extensively in terms of enteric coated tablets but haven’t been explored in as much detail when molecularly dispersed with a drug as in case of ASDs. Literature shows not all ASDs are able to improve bioavailability of drugs. Such a failure to provide bioavailability advantage via certain ASDs could come from a randomized drug and polymer selection in the preformulation stage of drug product development which could fundamentally arise from the lack of understanding of the release mechanisms of ASDs. Given that HPMCAS is one of the most popularly used polymers for spray drying of ASDs in the pharmaceutical industry, investigating the release mechanisms of HPMCAS-based ASDs is critical. In this study, some of the key formulation design factors, such as drug-polymer interactions, different grades of polymer as well as dissolution media factors such as buffer capacity that impact the release performance of HPMCAS-based ASDs have been investigated. The results from this study are expected to contribute to the fundamental understanding of the failure mechanisms of HPMCAS-based ASDs, reducing empirical screening of drugs during the preformulation stage of the product development and enhance the success rate of ASDs.</p>