When insulin was orally administered as a capsule containing Carbopol
934P (CP), freeze-dried sodium salt of CP (FNaCP), or lactose to diabe
tic 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) 40000 (FD-40), and inhibited the enzymati
c degradation of insulin to almost the same extent. FNaCP and CP in so
lution 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. C
P formed a swollen gel layer at the boundary between the medium and th
e capsule, which was a barrier for the drug release, but FNaCP did not
, as described in a previous paper (Nakanishi et al., 1998. Chem. Phar
m. Bull.171-173). Since the improving effects of FNaCP and CP in solut
ion were almost the same, the difference in the effects of these two p
olymers on insulin release is thought to be due to the existence of th
e barrier to the insulin release from the capsules. In conclusion, FNa
CP is a useful adjuvant for enabling the intestinal absorption of pept
ide drugs in a solid formulation such as capsules. (C) 1997 Elsevier S
cience B.V. All rights reserved.