Development and characterization of a novel peroral peptide drug delivery system

Novel drug delivery systems were developed for peroral administration of pe ptide and protein drugs for site specific mechanical fixation at the gut wa ll and with specific release patterns. These so-called shuttle systems were designed by using superporous hydrogels (SPH) and SPH composite (SPHC) as the conveyor of a con which contained the model compound N-alpha -benzoyl-L arginine ethylester (BAEE). Two different types of shuttle systems were ev aluated. (a) core inside the shuttle system, and (b) con attached to the su rface of shuttle system. Each of these systems was made of two parts: (1) t he conveyor system made of SPHC which is used for keeping the dosage form a t specific site(s) of the GI tract by mechanical interaction of the dosage form with the intestinal membranes, and (2) the cure containing the active ingredient and incorporated in the conveyor system. The effect of formulati on composition of the core on the release profile of BAEE was investigated by changing the type and amount of excipients in the formulations. In addit ion, the effect of various enteric-coat layers on the release profile and d issolving of the dosage form was investigated. The systems were also charac terized for trypsin inactivation and Ca2+ binding. The release profile of B AEE from the core formulation consisting of PEG 6000 microparticles or smal l tablets showed the desired burst release. When these core formulations we re incorporated into the conveyor system made of SPH and SPHC. a suitable t ime-controlled release profile was obtained. Changing the type, concentrati on and thickness of the enteric-coat layer influenced the starting time of BAEE release from the dosage form, which indicates the necessary lag time f or dissolving of the dosage form at any desired specific site of drug absor ption in the intestine. Both SPH and SPHC were found to partly inhibit the activity of trypsin, due to two mechanisms: Ca2+ binding and entrapment of the enzyme in these polymers. In conclusion, the presently developed delive ry systems demonstrate suitable in vitro characteristics with an appropriat e time-controlled release profile, making these systems very promising for effective peroral delivery of peptide and protein drugs. (C) 2001 Elsevier Science B.V. All rights reserved.