Impact of Swelling of Spray Dried Dispersions in Dissolution Media on their Dissolution: An Investigation Based on UV Imaging

Abstract

Impact of SDD-dissolution medium interactions on the swelling and dissolution of spray dried dispersions (SDDs) was investigated using UV imaging by monitoring SDD swelling in situ, along with correlating of the swelling with the micro-dissolution and intrinsic dissolution of SDDs. SDDs of ketoconazole or indomethacin with three polymers: polyvinylpyrrolidone (PVP), hydroxypropyl cellulose (HPC), and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were prepared for the study. Dissolution media employed for assessing swelling and dissolution include water, acetate buffer, phosphate buffer, fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF), in which influence of polymers and drugs together with the physical-chemical properties of dissolution media (pH, and the presence of sodium taurocholate and lecithin) on SDD swelling and dissolution was evaluated. It appears that hydrophilic and hydrophobic properties of polymers can significantly impact SDD swelling and thus the dissolution. Furthermore, properties of dissolution media such as pH as well as presence of bile salts and lecithin seems to affect SDD swelling and dissolution as well. Throughout the text, thermodynamic swelling of polymers was used to interpret SDD dissolution behavior. Finally, practical implication of polymer swelling on dissolution was discussed.