D-optimal Design and Development of Microemulsion Based Transungual Drug Delivery Formulation of Ciclopirox Olamine for Treatment of Onychomycosis

Abstract

The objective of the present study was to design and develop a microemulsion based transungual drug delivery formulation of ciclopirox olamine using colloidal carrier for treatment of onychomycosis. Capmul PG8 was selected as oil phase due to the high solubility of ciclopirox in it as compared to other oils and Cremophor EL and Transcutol P were used as surfactant and cosurfactant respectively. Pseudoternary phase diagrams were constructed using different ratio of S mix (surfactant:cosurfactant). The phase diagram obtained from 1:3 ratio showed largest microemulsion region. The construction of microemulsion was further optimized by D-optimal mixture design, taking oil, S mix and water as independent variables and globule size, transungual flux, and nail drug loading as response variables. Mathematical equations and response surface plots were used to correlate the dependent and independent variables. The optimized composition of microemulsion was predicted by numerical optimization technique on the basis of the highest desirability value. The predicted optimized microemulsion which contained 2% oil, 40% S mix , and 58% water was incorporated into Carbopol 940 The human nail plate is the most resistant barrier of the nail structure for drug penetration and therefore it is very difficult to deliver drug through nail in transungual infections [1] . Onychomycosis, also known as tinea unguium, is the most common nail fungal disease affecting approximately 14% of the general population and 48% aged population [2][3][4] . It affects one or more components of nail apparatus, including the nail plate, the nail matrix, and the nail bed.In the treatment of onychomycosis, the oral antifungal drug therapy remains the only choice due to deepseated persistent nature of the infectious fungi and limitation of topical route of drug administration due to poor drug permeation through nail plate [5,6] . A longduration oral antifungal therapy is, however, required to achieve therapeutic drug concentration in nail plate due to limited blood circulation at this site. This is often associated with serious side effects, drug interactions, and high recurrence rates. The problem of adverse effects of oral antifungal drug therapy can only be overcome if the drug delivery through nail plate could be realized [6] .The human nail plate is a highly ordered and dense epidermal structure grossly made up of three distinct layers -a thin dorsal lamina, the thicker intermediate lamina, and a ventral layer from the nail bed ( fig.1a). It composed of ~80% sulfur-rich α-keratin, 10-30%

Conidial Emulsion Formulation and Thermal Storability of Metarhizium anisopliae against Red Palm Weevil, Rhynchophorusferrugineus Olivier (Coleoptera: Dryophthoridae)

“…Emulsion formation was performed by admixing compatible oils and non-ionic surfactants with the least fungal growth inhibitory effect. The method was based on spontaneous or vortex-assisted emulsification as described by Chouhan & Saini [ 17 ]. In brief, surfactants were either used alone or blended according to the required hydrophile–lipophile balance (HLB) value for oils.…”

Design, Optimization, Manufacture and Characterization of Efavirenz-Loaded Flaxseed Oil Nanoemulsions

“…The pseudo-binary pre-concentrates mixtures contained no additional water. To minimize this effect, 500 mL of >98% ethanol was poured in a Schott Duran bottle (DWK Life Sciences, Hattenbergstr, Mainz, Germany) containing 300 g of 3A and 4A (1:1) m/m molecular sieve pellets from (B & M Scientific, Cape Town, South Africa), sealed and kept under air-conditioned laboratory room temperature for 7 days for further dehydration [ 31 , 32 ]. The ethanol was then degassed under vacuum with the aid of a Model A-2S Eyela aspirator degasser (Rikakikai Co., Ltd., Tokyo, Japan) and filtered through a 0.45-µm HVLP Durapore ® membrane filter (Millipore ® Corporation, Bedford, MA, USA) prior to use.…”

Development of ionic liquid microemulsion for transdermal delivery of a chemotherapeutic agent

“…The microemulsion formulation is a complex mixture of oil, surfactant, cosurfactant, water, and drug and the majority of its properties are dependent upon the droplet size of the internal phase [32,33]. Figure 1b, c, d reveals a pseudo-ternary phase diagram of 5-FU microemulsion with Tween 80, IPA, oleic acid, and water at room temperature.…”