Laboratory of Pharmaceutical, Chemical and Pharmacological Drug Development LR12ES09, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Laboratory of Applied Pharmacognosy, Institut Malgache de Recherches Appliquées, Fondation Albert et Suzanne RAKOTO-RATSIMAMANGA, Antananarivo, Madagascar.
J Pharm Pharmacol. 2020 Jul;72(7):889-896. doi: 10.1111/jphp.13265. Epub 2020 Apr 15.
This study investigates the effectiveness of self-nanoemulsifying drug delivery system (SNEDDS) in improving voriconazole transcorneal permeability.
Voriconazole-SNEDDS was prepared with isopropyl myristate, PEG 400, Tween 80 and Span 80 and was subjected for physicochemical characterization after reconstitution with NaCl 0.9% (1/9; v/v). In-vitro antifungal activity was assessed and compared with the marketed formulation. In-vivo studies, namely ocular irritation test via modified Draize test and pharmacokinetic study, were investigated using rabbit as animal model.
Voriconazole-SNEDDS presented a droplet size of 21.353 ± 0.065 nm, a polydispersity index of 0.123 ± 0.003, a pH of 7.205 ± 0.006 and an osmolarity of 342.667 ± 2.517 mOsmol/l after reconstitution with NaCl 0.9%. Voriconazole-SNEDDS minimum inhibitory concentration (MIC ) was similar to the one of marketed formulation for Candida species while it was significantly lower (P < 0.001) for Aspergillus fumigatus. Draize test revealed that Voriconazole-SNEDDS was safe for ocular administration. Voriconazole maximum concentration (5.577 ± 0.852 µg/ml) from SNEDDS was higher than marketed formulation (C = 4.307 ± 0.623 µg/ml), and the T was delayed to 2 h. The area under the concentration-time curve value of Voriconazole-SNEDDS was improved by 2.419-fold.
Our results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery and this encourages further clinical studies.
本研究旨在探讨自微乳药物传递系统（SNEDDS）提高伏立康唑经角膜通透性的效果。
采用肉豆蔻酸异丙酯、聚乙二醇 400、吐温 80 和司盘 80 制备伏立康唑 SNEDDS，并用 0.9%氯化钠（1/9；v/v）重构成混悬液后进行理化性质表征。评估其体外抗真菌活性，并与市售制剂进行比较。采用兔作为动物模型，进行体内研究，即改良 Draize 眼刺激性试验和药代动力学研究。
伏立康唑 SNEDDS 用 0.9%氯化钠重构成混悬液后，粒径为 21.353±0.065nm，多分散指数为 0.123±0.003，pH 值为 7.205±0.006，渗透压为 342.667±2.517mOsmol/l。SNEDDS 的伏立康唑最低抑菌浓度（MIC）与市售制剂对念珠菌相似，而对烟曲霉则显著降低（P<0.001）。Draize 试验表明，伏立康唑 SNEDDS 眼部给药安全。SNEDDS 的伏立康唑最大浓度（5.577±0.852µg/ml）高于市售制剂（C=4.307±0.623µg/ml），T 延迟至 2 小时。伏立康唑 SNEDDS 的浓度-时间曲线下面积值提高了 2.419 倍。
我们的研究结果表明，SNEDDS 是一种有前途的伏立康唑眼部传递载体，这鼓励进一步的临床研究。
