Comprehensive evaluation of polymer types and ratios in Spray-Dried Dispersions: Compaction, Dissolution, and physical stability

Abstract

Amorphous solid dispersion (ASD) is a well-established strategy for enhancing the solubility and bioavailability of poorly soluble drugs. A significant portion of ASD products are in tablet form. However, the influence of common polymers and drug loading on the manufacturability of ASD tablets remains underexplored. This study focuses on investigating spray-dried ASDs from a tableting perspective by evaluating their physiochemical and mechanical properties. Itraconazole (ITZ) and indomethacin (IND), at the drug loadings ranging from 10% to 50%, were prepared with two polymers, hydroxypropyl methylcellulose acetate succinate (HPMCAS) and polyvinylpyrrolidone (PVP), serving as representative systems. Our findings revealed that increasing the drug loading resulted in a decreased surface area in ITZ-HPMCAS, IND-HPMCAS, and IND-PVP ASDs. However, this trend was not observed in ITZ-PVP dispersions, possibly due to the morphological disparities. Compaction results demonstrated that tabletability improved with decreasing drug loadings, except for ITZ-PVP dispersions. A partial least square analysis underscored particle surface area as the key factor influencing the tensile strength of ASD tablets. Additionally, our study disclosed that ITZ-PVP ASDs exhibited the worst release profiles and stability performance. The comprehensive journey from characterizing ASD particles to analyzing their compaction behavior and investigating drug release and physical stability offered profound insights into the attributes crucial for the downstream processing of amorphous pharmaceuticals.