Basic studies on bioadhesive delivery systems for peptide and protein drugs

Abstract

We have been evaluating the influence of different drying methods and of ionic crosslinkers on adhesive strength, cohesiveness as well as release behaviour of bioadhesive polymers. Chitosan-EDTA and carbomer were ionically crosslinked via 1,8-diaminooctane or l-lysine. The resulting polymers were either lyophilised or precipitated in acetone and air-dried. Tablets made of these pre-treated polymers (66.7%), mannitol (30%), and the model drug insulin (3.3%) were investigated in vitro. Whereas tablets containing the precipitated and air-dried chitosan-EDTA or carbomer exhibited under our experimental conditions an adhesive strength of 93.2±15.6 and 93.1±17.3 mN, it was determined to be 57.7±9.5 and 56.1±6.7 mN (mean±S.D.; n=5) for tablets of the same but lyophilised polymers, respectively. The use of ionic crosslinkers led also to a significant reduction in the bioadhesiveness of the dosage form. Furthermore, the stability of tablets could be strongly increased by using ionic crosslinkers and/or the precipitated and air-dried form of chitosan-EDTA or carbomer. Due to the use of ionic crosslinkers, the release rate of insulin was strongly reduced. The results represent helpful basic information for the development of peroral (poly)peptide delivery systems based on bioadhesive polymers.