title: Transungual Delivery of Ketoconazole Nanoemulgel for the Effective Management of Onychomycosis.
abstract: 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 (NEG1) 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, NEG1and 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, NEG1and 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 NEG1on 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.
authors: Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors: Asiya
authors: A
authors: Mahtab
authors: Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India. md.anwar2008@gmail.com.
authors: Mohammed
authors: M
authors: Anwar
authors: Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors: Neha
authors: N
authors: Mallick
authors: Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors: Zrien
authors: Z
authors: Naz
authors: Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors: Gaurav K
authors: GK
authors: Jain
authors: Nanoformulation Research Laboratory, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India. farhanja_2000@yahoo.com.
authors: Farhan J
authors: FJ
authors: Ahmad
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D002176:Candida albicans / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry; D005782:Gels / Q000008:administration & dosage; D007654:Ketoconazole / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D014009:Onychomycosis / Q000188:drug therapy*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D014249:Trichophyton / Q000187:drug effects; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D005782:Gels; D007654:Ketoconazole
keywords: ketoconazole; nanoemulgel; nanoemulsion; onychomycosis; transungual drug delivery