Impact\nof HPMCAS Grade on the Release of Weakly Basic\nDrugs from Amorphous Solid Dispersions

Oppositely charged species can form electrostatic interactions\nin aqueous solution, and these may lead to reduced solubility of the\ninteracting components. Herein, insoluble complex formation between\nthe lipophilic weakly basic drugs, cinnarizine or loratadine, and\nthe enteric polymer, hydroxypropyl methylcellulose acetate succinate\n(HPMCAS), was studied and used to better understand drug and polymer\nrelease from their corresponding amorphous solid dispersions (ASDs).\nSurface area normalized release experiments were performed at various\npH conditions for three different grades of HPMCAS, LF, MF and HF,\nas well as their ASDs. Both polymer and drug release rates were measured\nfor the ASDs. Complexation tendency was evaluated by measuring the\nextent of polymer loss from the aqueous phase in the presence of the\ndrug. Results showed that release from ASDs with HPMCAS-LF was less\nimpacted by the presence of a cationic form of the drug than ASDs\nprepared with the HF grade. Furthermore, an increase in pH, leading\nto a reduction in the extent of ionized drug also led to an improvement\nin release rate. These observations provide a baseline to understand\nthe role of drug–polymer electrostatic interactions on release\nfrom ASDs formulated with HPMCAS. Future studies should focus on adding\ncomplexity to media conditions by employing simulated intestinal fluids\nwith solubilizing components.