论文信息 - Physicochemical characterization and evaluation of a microemulsion system for oral delivery of cyclosporin A

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

Abstract 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 ® ) as an oil, polyoxyethylated castor oil (Cremophor EL ® ) as a surfactant, Transcutol ® 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 ® to Trancutol ® . The solubility of cyclosporin A in microemulsion systems reached the maximum with 2:1 mixture of Cremophor EL ® and Trancutol ® . The dispersion rate of oil–surfactant–cosurfactant mixture with varying ratios of Cremophor EL ® to Trancutol ® in aqueous media assuming the condition of gastric fluid decreased with the increase of Cremophor EL ® to Trancutol ® weight ratio. The droplet size of microemulsion without cyclosporin A was decreased with the increase of Cremophor EL ® 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 ® :Transcutol ® :Captex 355 ® , 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 ® . No significant difference of C max and AUC was observed between this microemulsion system and Sandimmun Neoral ® . The absolute bioavailability of cyclosporin A loaded in this microemulsion system was increased about 3.3 and 1.25 fold compared with Sandimmun ® and Sandimmun Neoral ® . The enhanced bioavailability of cyclosporin A loaded in this microemulsion system might be due to the reduced droplet size of microemulsion systems.

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