The percutaneous penetration of R-(+)- and S-(-)-propranolol (PL) through rat excised skin was investigated in vitro. The flux of S-(-)-PL after application to normal skin was high compared with that of R-(+)-PL. On the other hand, in damaged rat skin, the flux of R-(+)-PL was almost equivalent to that of S-(-)-PL. It is suggested that there is an enantiomeric difference between S-(-)- and R-(+)-PL in terms of penetration through rat stratum corneum.

No abstract

The enhancing effect of cetyl lactate (CL) on the percutaneous absorption of indomethacin (ID) from test solutions in propylene glycol (PG) was investigated by using the abdominal skin of rats in vivo. The percutaneous absorption rate of ID from 1 or 3% CL-PG test solution through the intact skin of rats was observed to be faster than that from the control solution (without CL). The bioavailability of ID was about 0.04% for the control solution, 2.2% for 1% CL-PG and 6.8% for 3% CL-PG test solutions. These results suggest that CL functions as an enhancer for the percutaneous absorption of ID. Furthermore, marked enhancing effects on percutaneous absorption of ID were obtained at a concentration greater than 1% CL in PG. In order to elucidate the mode of action of CL as an absorption enhancer, the percutaneous absorption of ID from the control solution and 3% CL-PG test solution through damaged skin from which the stratum corneum had been stripped was additionally investigated. It was confirmed that CL acts on the stratum corneum to produce its effect.

No abstract

Carbopol 934P (CP) is a mucoadhesive polymer which has been investigated as a useful adjuvant for bioadhesive drug delivery system. However, since the drug release rate from the solid formulation of CP is slow, it is difficult to take advantage of the polymer's mucoadhesive property in oral administration of fast-acting drugs. In this study, we prepared freeze-dried sodium salt of CP (FNaCP) in order to improve drug release from the formulation of CP. The drug release rate from the formulation of FNaCP was much faster than that of CP: the rate from the formulation of CP in JP XIII 1st fluid (pH 1.2) was faster than in JP XIII 2nd fluid (pH 6.8). To determine the cause of rapid drug release from FNaCP capsules, the change of CP gel properties with pH and ionic strength was investigated. Experimental results indicated that CP forms a swollen gel layer, a drug release barrier between the formulation of CP and the bulk release media. FNaCP was also thought to disperse rapidly in the 1st and 2nd fluids without formation of the swollen gel layer. In conclusion, since FNaCP improves the drug release rate from the solid CP formulation, it could be a useful adjuvant of an oral bioadhesive drug delivery system.