Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junin 954, 1113, Buenos Aires, Argentina.
AAPS PharmSciTech. 2010 Jun;11(2):986-93. doi: 10.1208/s12249-010-9457-1. Epub 2010 Jun 3.
The present study aimed to evaluate different dosage forms, emulsions, emulgels, lipogels, and thickened microemulsion-based hydrogel, as fluconazole topical delivery systems with the purpose of determining a formulation with the capacity to deliver the whole active compound and maintain it within the skin so as to be considered a useful formulation either for topical mycosis treatment or as adjuvant in a combined therapy for Cutaneous Leishmaniasis. Propylene glycol and diethyleneglycol monoethyl ether were used for each dosage form as solvent for the drug and also as penetration enhancers. In vitro drug release after application of a clinically relevant dose of each formulation was evaluated and then microemulsions and lipogels were selected for the in vitro penetration and permeation study. Membranes of mixed cellulose esters and full-thickness pig ear skin were used for the in vitro studies. Candida albicans was used to test antifungal activity. A microemulsion containing diethyleneglycol monoethyl ether was found to be the optimum formulation as it was able to deliver the whole contained dose and enhance its skin penetration. Also this microemulsion showed the best performance in the antifungal activity test compared with the one containing propylene glycol. These results are according to previous reports of the advantages of microemulsions for topical administration and they are very promising for further clinical evaluation.
本研究旨在评估不同的剂型,如乳剂、乳凝胶、脂肪凝胶和增稠的微乳液基水凝胶,作为氟康唑的局部递药系统,目的是确定一种能够输送全部活性化合物并将其维持在皮肤内的制剂,以便被认为是一种有用的制剂,无论是用于局部真菌感染的治疗还是作为联合治疗皮肤利什曼病的辅助治疗。对于每种剂型,均使用丙二醇和二乙二醇单乙醚作为药物的溶剂,同时也作为渗透增强剂。评估了每种制剂临床相关剂量给药后的体外药物释放情况,然后选择微乳液和脂肪凝胶进行体外渗透和渗透研究。用于体外研究的是混合纤维素酯膜和全厚猪耳皮肤。使用白色念珠菌来测试抗真菌活性。发现含有二乙二醇单乙醚的微乳液是最佳制剂,因为它能够输送全部包含的剂量并增强其皮肤渗透。与含有丙二醇的微乳液相比,该微乳液在抗真菌活性测试中表现最佳。这些结果与微乳液用于局部给药的先前报道的优势一致,并且非常有希望进行进一步的临床评估。