Development and in vitro evaluation of a drug delivery system based on chitosan-EDTA BBI conjugate

In this study a (poly)peptide drug delivery system providing a protective e ffect towards serine pancreatic proteases was generated. Tablets containing insulin (3.3%), chitosan-EDTA (56.7%), chitosan-EDTA Bowman-Birk Inhibitor (= BBI) conjugate (10%) and mannitol (30%) were homogenised in a mortar an d compressed to tablets. The protective effect of this dosage form for the incorporated model drug was evaluated in,vitro. Tablets were therefore incu bated with an artificial intestinal fluid containing trypsin (1350 spectrop hotometric BAEE units/ml), chymotrypsin (3.6 BTEE units/ml) and elastase (0 .14 succinyl-Ala-Ala-Ala-p-nitroanilide units/ml) for 4.5 h at 37 degrees C , Following analysis of the dosage form demonstrated that 58.6 +/- 26.8% (m ean +/- SD; n = 3) insulin in lateral Darts and 44.4 +/- 12.4% (mean +/- SD ; n = 3) insulin in inner parts of the swollen carrier-matrix were degraded , whereas insulin was completely metabolised in lateral parts and by 90.3 /- 12.5% (mean +/- SD; n = 3) ill inner parts of tablets without the chitos an-EDTA BBI conjugate. As chitosan-EDTA also provides a protective effect t owards zinc-dependent proteases, the delivery system described in this stud y should therefore guarantee a protection towards the most abundant intesti nal proteases. It might be a promising formulation for the peroral administ ration of peptide and protein drugs.