Mahtab Asiya, Anwar Mohammed, Mallick Neha, Naz Zrien, Jain Gaurav K, Ahmad Farhan J
Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
AAPS PharmSciTech. 2016 Dec;17(6):1477-1490. doi: 10.1208/s12249-016-0488-0. Epub 2016 Feb 8.
Ketoconazole (KCZ) nanoemulgel containing permeation enhancer was formulated as a vehicle for transungual drug delivery, and its efficacy to inhibit the growth of onychomycotic dermatophytes was investigated in vitro. Different components of oil-in-water nanoemulsions were moderately agitated by classical titration method and passed through a high-pressure homogenizer to formulate various nanoemulsions, which were further identified by constructing pseudo-ternary phase diagrams. Stress-stability testing was carried out for the nanoemulsions, and those that passed these tests were characterized for mean droplet size, zeta potential, morphology, pH, refractive index, viscosity and transmittance. Mean droplet size and zeta potential of the optimized nanoemulsion (NE3) were found to be 77.52 ± 0.92 nm (polydispersity index (PDI) = 0.128 ± 0.035) and -5.44 ± 0.67 mV, respectively. Optimized nanoemulsion was converted into nanoemulgel (NEG) with 1% (w/w) of gelling agent (Carbopol® Ultrez 21) and 1%-2% (v/v) thioglycolic acid as permeation enhancer, and evaluated for pH, viscosity, spreadability, extrudability, tensile strength and bio-adhesion measurement. In vitro cumulative drug released at the end of 24 h from NE3, NEG and drug suspension were found to be 98.87 ± 1.29, 84.42 ± 2.78% and 54.86 ± 2.19%, respectively. Ex vivo transungual permeation values for KCZ through goat hooves from NE3, NEG and drug suspension were found to be 62.49 ± 2.98, 77.54 ± 2.88% and 38.54 ± 2.54%, respectively, in 24 h. The antifungal effect of NEG on Trichophyton rubrum and Candida albicans showed a significant (p < 0.05) zone of inhibition as compared to drug solution. Skin irritation and histopathology studies on rat skin showed the safe topical use and enhanced permeation of formulated nanoemulgel.
含有渗透促进剂的酮康唑（KCZ）纳米乳凝胶被制备为经甲给药的载体，并在体外研究了其抑制甲癣皮肤癣菌生长的功效。采用经典滴定法对水包油纳米乳的不同组分进行适度搅拌，然后通过高压均质机制备各种纳米乳，通过构建伪三元相图进一步鉴定。对纳米乳进行了应力稳定性测试，通过测试的纳米乳对其平均粒径、ζ电位、形态、pH值、折射率、粘度和透光率进行了表征。发现优化后的纳米乳（NE3）的平均粒径和ζ电位分别为77.52±0.92nm（多分散指数（PDI）=0.128±0.035）和-5.44±0.67mV。将优化后的纳米乳与1%（w/w）的胶凝剂（卡波姆®优立通21）和1%-2%（v/v）的巯基乙酸作为渗透促进剂转化为纳米乳凝胶（NEG），并对其pH值、粘度、铺展性、挤出性、拉伸强度和生物粘附性进行了评估。在24小时结束时，NE3、NEG和药物悬浮液的体外累积药物释放率分别为98.87±1.29%、84.42±2.78%和54.86±2.19%。在24小时内，通过山羊蹄甲的酮康唑从NE3、NEG和药物悬浮液的离体经甲渗透值分别为62.49±2.98%、77.54±2.88%和38.54±2.54%。与药物溶液相比，NEG对红色毛癣菌和白色念珠菌的抗真菌作用显示出显著（p<0.05）的抑菌圈。对大鼠皮肤的皮肤刺激性和组织病理学研究表明，所制备的纳米乳凝胶局部使用安全且渗透增强。
