Impact of HPMCAS Grade on the Release of Weakly Basic Drugs from Amorphous Solid Dispersions.

Abstract

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