1 Faculty of Pharmacy, Federal University of Minas Gerais , Belo Horizonte, Brazil .
J Ocul Pharmacol Ther. 2014 Feb;30(1):59-65. doi: 10.1089/jop.2013.0128. Epub 2013 Nov 7.
Tacrolimus is a potent immunosuppressive agent with limited corneal penetration. Microemulsions can increase the drug solubility and enhance drug absorption in the eye. This work aimed to develop a tacrolimus microemulsion as well as to characterize and to evaluate its ocular tolerance and pharmacokinetics after topical application in rabbits.
The microemulsion was prepared by the titration with the cosurfactant technique and its physical-chemical parameters and stability were determined. The cytotoxicity was evaluated using the corneal epithelium and conjunctiva cell lines. The ocular pharmacokinetic parameters in rabbits were determined and compared with that obtained after instillation of tacrolimus suspension.
The microemulsion containing tacrolimus was successfully developed. It was nonirritating to rabbits' eyes and it was also not toxic to the corneal and conjunctival cells. When compared to the suspension, the microemulsion containing tacrolimus presented higher values of AUC (2,912.5±245.4 min.ng/mL vs. 1,669.8±93 min.ng/mL) and Cmax (26.8±2.3 ng/mL vs. 20.7±2.8 ng/mL). On the other hand, the Cl/F value was smaller when compared to the suspension that may decrease the number of applications of eye drops.
The developed microemulsion could be an alternative to reduce the systemic adverse effects of tacrolimus and, consequently, increase the patient compliance to the treatment.
他克莫司是一种具有有限角膜穿透性的强效免疫抑制剂。微乳可以增加药物的溶解度并增强药物在眼部的吸收。本研究旨在开发一种他克莫司微乳，并对其进行特征描述和评价，以及考察其在兔眼局部应用后的眼耐受性和药代动力学。
采用添加助溶剂的滴定法制备微乳，并测定其物理化学参数和稳定性。采用角膜上皮细胞和结膜细胞系评估细胞毒性。在兔体内测定眼部药代动力学参数，并与滴注他克莫司混悬液后的药代动力学参数进行比较。
成功开发了含他克莫司的微乳。该微乳对兔眼无刺激性，对角膜和结膜细胞也无毒性。与混悬液相比，含他克莫司的微乳具有更高的 AUC（2,912.5±245.4 min.ng/mL 对 1,669.8±93 min.ng/mL）和 Cmax（26.8±2.3 ng/mL 对 20.7±2.8 ng/mL）值。另一方面，与混悬液相比，微乳的 Cl/F 值较小，这可能会减少滴眼次数。
所开发的微乳可作为减少他克莫司全身不良反应的一种替代方法，从而提高患者对治疗的依从性。
