Lyophilized Chitosan-Based Hydrogels as a Potential Stimuli-Responsive Carrier System for Anti-Inflammatory Drugs:...

Poor aqueous solubility and consequently low bioavailability of various NSAIDs (non-steroidal anti-inflammatory drugs) usually result in high and multiple dosing with potentially serious side effects. Therefore, systems for the effective transport of NSAIDs through the GIT (gastrointestinal tract), ensuring enhanced bioavailability, remain in high demand. In the present work, we studied chitosan (CS) hydrogel lyophilizates as carrier systems for a model NSAID, namely ibuprofen (IBU). The CS-IBU lyophilizates were prepared from homogeneous or heterogeneous CS-IBU hydrogels to assess their influence on the resulting lyophilizate microstructure and IBU dissolution profiles. To gain a complex view of the CS-IBU behavior and its practical consequences, dissolution profiles of free IBU (reference) and CS-associated IBU (CS-IBU) were examined and compared to each other at variable pH (1.2 and 6.5) in two separate dissolution systems and in one discontinuous dissolution system mimicking GIT conditions. The results of dissolution experiments were supported by kinetic model data. This study demonstrated that the dissolution of IBU from the CS-IBU lyophilizates is affected by two main pH-dependent competitive effects; i.e., dissolved CS acts as an IBU solubilizer and the undissolved CS matrix serves as an IBU trap, which could be used in the rational design of innovative stimuli (pH)-responsive oral dosage forms of IBU.