Physicochemical characterization and evaluation of a microemulsion system for oral delivery of cyclosporin A

The purpose of this study was to improve the solubility and enhance the bioavailability of poorly water-soluble cyclosporin A loaded in o/w microemulsion systems. Microemulsions with varying weight ratios of surfactant to cosurfactant were prepared using caprylic/capric triglyceride (Captex 355(R)) as an oil, polyoxyethylated castor oil (Cremophor EL(R)) as a surfactant, Transcutol(R) as a cosurfactant and saline. The area of o/w microemulsion region in pseudo-ternary phase diagram was increased with increasing ratio of Cremophor EL(R) to Trancutol(R). The solubility of cyclosporin A in microemulsion systems reached the maximum with 2:1 mixture of Cremophor EL(R) and Trancutol(R). The dispersion rate of oil-surfactant-cosurfactant mixture with varying ratios of Cremophor EL(R) to Trancutol(R) in aqueous media assuming the condition of gastric fluid decreased with the increase of Cremophor EL(R) to Trancutol(R) weight ratio. The droplet size of microemulsion without cyclosporin A was decreased with the increase of Cremophor EL(R) content. The droplet size increased on increasing the incorporation of cyclosporin A. The droplet size of cyclosporin A loaded microemulsion was minimized with microemulsions prepared with 2:1 mixture of surfactant to cosurfactant (Cremophor EL(R):Transcutol(R):Captex 355(R), 10:5:4). The maximal blood concentration (C-max) of cyclosporin A and the area under the drug concentration-time curve (AUC) after oral administration of this cyclosporin A loaded microemulsion was 3.5 and 3.3 fold increased compared with Sandimmun(R). No significant difference of C-max and AUC was observed between this microemulsion system and Sandimmun Neoral(R). The absolute bioavailability of cyclosporin A loaded in this microemulsion system was increased about 3.3 and 1.25 fold compared with Sandimmun(R) and Sandimmun Neoral(R). The enhanced bioavailability of cyclosporin A loaded in this microemulsion system might be due to the reduced droplet size of microemulsion systems. (C) 1998 Elsevier Science Ireland Ltd.