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Enhanced efficacy of triprolidine by transdermal application of the EVA matrix system in rabbits and rats.

The bioavailability of triprolidine from the ethylene vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether was studied to determine the feasibility of enhanced transdermal delivery of triprolidine in rabbits. The antihistamine effects were also confirmed to determine the percutaneous absorption of triprolidine from the EVA matrix system containing a penetration enhancer and plasticizer in rats. The triprolidine-EVA matrix (50mg/kg) was applied to the abdominal skin of rabbits. Blood samples were collected via the femoral artery for 36 h and the plasma concentrations of triprolidine were determined by HPLC. The pharmacokinetic parameters were calculated using the LAGRAN computer program. The area under the curve(AUC) was significantly higher in the enhancer group (4582+/-1456 ng/mL h) than that (2958+/-997 ng/mL h) in the control group (P<0.05), showing an approximate 155% increased bioavailability. The average Cmax in the enhancer group (241+/-46.5 ng/mL) was significantly higher than that in the control group (198+/-28.9 ng/mL), (P<0.05). The mean Tmax in the enhancer group (8.0+/-2.57 h) was higher than that in the control group (6.0+/-2.24 h, but this was not statistically significantly. The relative bioavailability of triprolidine in the transdermal application was 35.9% in the control group and 55.6% in the enhancer group compared comparing with that after oral administration. As the triprolidine-EVA matrix, which contains polyoxyethylene-2-oleyl ether as an enhancer and triethyl citrate as a plasticizer was administered to the rabbits via the transdermal routes, the relative bioavailability increased approximately 1.55 fold compared with that in the control group, showing a relatively constant, sustained blood concentration with minimal fluctuation. The antihistamine effect was determined using the Evans blue dye procedure by comparing the changes in the vascular permeability increase following the transdermal application. The vascular permeability increase was reduced significantly by the transdermal application of the EVA-triprolidine system containing triethyl citrate and polyoxyethylene-2-oleyl ether. These results show that the plasticizer and penetration enhancer increase the skin permeation of triprolidine and the triprolidine-EVA matrix system could be developed as a transdermal delivery system providing the increased constant plasma concentration and antihistamine effects.[1]

References

  1. Enhanced efficacy of triprolidine by transdermal application of the EVA matrix system in rabbits and rats. Shin, S.C., Choi, J.S. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V. (2005) [Pubmed]
 
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