Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, 388421, Gujarat, India.
Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, 388421, Gujarat, India.
Colloids Surf B Biointerfaces. 2021 May;201:111652. doi: 10.1016/j.colsurfb.2021.111652. Epub 2021 Feb 19.
The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul® MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol® (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol® P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudo-ternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol® 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36±12.90μgcm) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.
由于局部制剂在指甲中的驻留时间较短，以及新一代抗真菌药物市场缺乏新型制剂，甲真菌病的治疗仍然是皮肤科医生面临的一大挑战。本研究旨在设计、开发、优化和评估微乳制剂，通过透皮途径有效递送达氟沙星，用于治疗甲真菌病。Capmul® MCM（辛酸/癸酸甘油酯）作为油相，Labrasol®（辛酸/癸酸聚氧乙烯-8 甘油酯）作为表面活性剂，Transcutol® P（二乙二醇单乙基醚）作为助表面活性剂，显示出更高的达氟沙星溶解度和表面活性剂-助表面活性剂混合物（Smix）溶解度，在伪三元相图中形成更高的微乳液区域。优化的微乳制剂含有 6%w/w 的油相、22.5%w/w 的表面活性剂、22.5%w/w 的助表面活性剂和 49%w/w 的去离子水，通过加入 1.0%w/w 的 Carbopol® 934 P 凝胶剂转化为凝胶制剂，并评估了 6 个月的稳定性。优化的微乳制剂液滴大小小于 100nm。体外渗透实验证实，与未观察到药物渗透滞后的参考制剂相比，达氟沙星从微乳制剂中的渗透得到了改善（346.36±12.90μgcm）。体外抗真菌研究数据表明，与达氟沙星局部溶液相比，该制剂对红色毛癣菌、须癣毛癣菌和白色念珠菌的抗真菌效果有所提高。此外，体外细胞毒性研究表明，在指甲细胞上应用制剂中使用的任何赋形剂均无毒性作用。因此，载有达氟沙星的微乳制剂可被视为治疗甲真菌病的有效疗法。
