Fusao Kaiho

Use of sodium salt of Carbopol 934P in oral peptide delivery

Abstract When insulin was orally administered as a capsule containing Carbopol 934P (CP), freeze-dried sodium salt of CP (FNaCP), or lactose to diabetic rats, FNaCP improved the intestinal absorption of insulin, whereas CP and lactose did not. In the in vitro experiments, FNaCP and CP in solution increased the mucoadhesion of the model compound, fluorescein isothiocyanate-dextran (FD) 40 000 (FD-40), and inhibited the enzymatic degradation of insulin to almost the same extent. FNaCP and CP in solution changed neither the membrane resistance nor the permeability of FD 4000 (FD-4) in the rat jejunum, indicating that an improvement of the paracellular peptide delivery did not take place in the jejunum. CP formed a swollen gel layer at the boundary between the medium and the capsule, which was a barrier for the drug release, but FNaCP did not, as described in a previous paper (Nakanishi et al., 1998. Chem. Pharm. Bull. 171–173). Since the improving effects of FNaCP and CP in solution were almost the same, the difference in the effects of these two polymers on insulin release is thought to be due to the existence of the barrier to the insulin release from the capsules. In conclusion, FNaCP is a useful adjuvant for enabling the intestinal absorption of peptide drugs in a solid formulation such as capsules.