Evaluation of Oil/Water-Type Cyclosporine Gel Ointment with Commercially Available Oral Solution

Abstract

Oil/water-type cyclosporine (CyA) hydrogel ointment was evaluated as a candidate for the percutaneous application of CyA. The physical properties and the permeation profiles of 2% w/w CyA gel ointment were compared with other CyA ointments. All ointments used in this study were prepared with commercially available CyA (Sandimmune) oral solution, unlike the ointment reported in the publication of by Mizoguchi et al. The gel ointment required a surfactant corresponding to 5–7% w/w to obtain fine uniform particles. Mean diameter of oily particles in the gel ointment was 8.75 μm. The permeation of CyA from the ointments was investigated by using the abdominal skin of hairless rats in vitro. The percutaneous permeation of CyA was observed to be influenced by a variety of ointment bases used and by the presence of a stratum corneum which plays a role as the main barrier. In intact skin, the extent of permeation from the gel ointment was almost equivalent to that from Mizoguchi's ointment, which used the raw CyA. No permeation was observed in ointment bases with either white petrolatum or hydrophilic petrolatum, indicating values under the limit of detection (78 ng/ml) of the high-performance liquid chromatographic method used in this study. On the other hand, in stripped skin, differences in flux value of each ointment were shown. Those values increased in the following order: Mizoguchi's ointment, white petrolatum, hydrogel, hydrophilic petrolatum. From these results, hydrogel ointment seemed to be applicable for various skin diseases which respond to CyA. Of the physical properties, spreadability and consistency showed that gel ointment was superior to Mizoguchi's ointment. In stability tests, the gel ointment was stable with regard to particle size and residual CyA for 4 weeks. These results suggested that the oil/water-type CyA hydrogel ointment prepared in a combination with hydrogel and commercially available oral solution was useful for practical hospital preparations, with good physical properties, permeability, and stability.