MUCOADHESIVE POLYMERS IN PERORAL PEPTIDE DRUG-DELIVERY .6. CARBOMER AND CHITOSAN IMPROVE THE INTESTINAL-ABSORPTION OF THE PEPTIDE DRUG BUSERELIN IN-VIVO

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carb omer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC93 4P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduoden ally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w /v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/ v)) mixture in rats. Results. All polymer preparation showed a statist ically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different po lymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934 P, 2,0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochlor ide (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosa n hydrochloride compared to C934P and FNaC934P indicates that for buse relin the intestinal transmucosal transport enhancing effect of the po lymer plays a more dominant role than the protection against proteases such as alpha-chymotrypsin. Conclusions. The mucoadhesive polymers ca rbomer 934P and chitosan hydrochloride are able to enhance the intesti nal absorption of buserelin in vivo in rats, and may therefore be prom ising excipients in peroral delivery systems for peptide drugs.