Peroral administration of enzymes: Strategies to improve the galenic of dosage forms for trypsin and bromelain

In this study, we investigated the presystemic metabolism of trypsin and br omelain and the influence of these proteolytic enzymes on the mucus layer c overing the gastrointestinal (GI) epithelia. In vitro studies demonstrated that 77.3% +/- 4.0% (mean +/- SD, n = 3) of trypsin is autodegraded within 2 hr, whereas autodegradation of bromelain was negligible. In contrast to t he metabolization of bromelain by all pancreatic serine proteases, trypsin is only degraded to some extent by elastase. Both therapeutically used enzy mes remained stable after incubation with an excised porcine mucosa, demons trating that proteolysis caused by brush border membrane-bound enzymes is n egligible. Trypsin and bromelain were highly mucolytic active, thereby redu cing the diffusion barrier based on the mucus gel layer. Strategies to impr ove the galenic of dosage forms for trypsin and bromelain include the use o f bioadhesive polymers such as hydroxyethylcellulose or slightly modified c hitosan-EDTA, providing strongly improved stability of these enzymes toward proteolytic degradation in vitro. The given information represents a good starting point to improve the galenic of dosage forms for orally administer ed proteolytic enzymes.