A dynamic in vitro model to evaluate the intestinal release behaviour of modified-release corticosteroid products

Corticosteroids form an important component of drug-based therapeutic strategies in both Crohn's disease and ulcerative colitis. Here, we investigated the intestinal release behaviour of two commonly-used corticosteroids - prednisolone and budesonide - from various commercial modified-release formulations. We evaluated the release characteristics using a novel in vitro model that simulates the dynamic intestinal environment by employing bicarbonate buffers representative of the conditions and contents of the gastrointestinal lumen. The performance of the model was validated with an in-house enteric dual layer prednisolone formulation (internal standard) where in vitro release behaviour closely correlated with in vivo targeting performance in humans. The commercial prednisolone product coated with the pH responsive polymer polyvinyl acetate phthalate released its payload promptly on transfer to the upper small intestinal compartment of the test. In contrast, the budesonide products, Entocort® and Budenofalk®, although showing differences in product performance and delayed release characteristics, both demonstrated some suggestion of extended release behaviour. The proposed dissolution method provided a realistic and discriminative in vitro assessment of the release of corticosteroids from different oral formulations. These results demonstrate that this model can be used to aid the rational design of products developed to target different sites of the gut.