Absorption of interferon alpha from patches in rats

Abstract

Interferon alpha (IFN-α), patch preparations composed of three layers, water-insoluble backing layer, drug containing layer with absorption enhancer and surface layer containing pH-dependent polymer were prepared. As absorption enhancer, three surfactants, Gelucire44/14 (Lauroyl macrogol-32 glycerides), Labrasol (Caprylocaproyl macrogol-8 glycerides) and HCO-60 (polyoxyethylated hydrogenerated castor oil) were used in preparing IFN-α patch preparations. The intestinal absorption of IFN-α was studied after the administration of test patch preparations into the rat jejunum, 50,000 IU/kg. The serum IFN-α levels were measured by an ELISA method and both Cmax and AUC were determined as the index of absorption of IFN-α. Gelucire44/14 preparation including Pharmasol for the stable solidification showed the higher Cmax, 7.66 ± 0.82 IU/ml, and AUC, 12.85 ± 1.49 IU h/ml, than Labrasol (6.51 ± 0.89 and 8.30 ± 1.34 IU h/ml) and HCO-60 (6.02 ± 1.14, 7.53 ± 1.84 IU h/ml) preparations, respectively. By comparing to the AUC obtained after s.c. injection of the same dose of IFN-α to rats, bioavailability (BA) was estimated to be 7.8% in Gelucire44/14 preparation. In vitro release study showed that the T50%s, the time when half of the formulated IFN-α is released from the patches, were 3.4 ± 0.1 min for HCO-60, 7.8 ± 0.1 min for Gelucire44/14 and 11.4 ± 0.1 min for Labrasol preparations. To study the effect of absorption site, Gelucire44/14 preparation was administered into the rat duodenum and ileum. However, there were not significant differences on AUC among the three absorption sites. By reducing the IFN-α dose from 50,000 to 25,000 IU/kg, the serum IFN-α levels vs time profile showed a tendency of dose-dependency. When the histological examination of small intestinal mucosa was carried out in this study, the small intestinal mucosa after the Gelucire44/14 patches administered and before it was administered, could not recognize impaired. From these results, the usefulness of oral patch system for the oral delivery of IFN-α has been proved in rats.