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The treatment of onychomycosis is a challenging task because of unique barrier properties of the nail plate which hampers the passage of antifungal drugs in a concentration required to eradicate the deeply seated causative fungi in the nail bed. In present investigation, application of hydroxypropyl-β-cyclodextrin (HP-β-CD) was established as an effective and nail friendly transungual drug permeation enhancer especially for poorly water soluble drugs using terbinafine hydrochloride as a poorly soluble drug. HP-β-CD significantly improves hydration of nail plates and increases solubility of terbinafine hydrochloride in the aqueous environment available therein, which leads to uninterrupted drug permeation through water filled pores of hydrogel-like structure of hydrated nail plates. A nail lacquer formulation was designed with an objective to deliver the drug in an effective concentration across nail plates, using HP-β-CD as a permeation enhancer. The formulations containing HP-β-CD showed higher flux than the control formulation in in vitro drug permeation study. The formulation containing 10% w/v of HP-β-CD showed maximum flux of 4.586 ± 0.08 μg/mL/cm2 as compared to the control flux of 0.868 ± 0.06 μg/mL/cm2. This finding supports application of HP-β-CD as an effective permeation enhancer for transungual delivery of terbinafine hydrochloride and possibly other poorly water soluble drugs where HP-β-CD can act as a solubilizer.

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%

A series of 2,3,4,9-tetrahydro-β-carboline tetrazole derivatives () have been synthesized utilizing the Ugi multicomponent reaction and were identified as potential antileishmanial chemotypes. Most of the screened derivatives exhibited significant activity against the promastigote (IC from 0.59 ± 0.35 to 31 ± 1.27 μM) and intracellular amastigote forms (IC from 1.57 ± 0.12 to 17.6 ± 0.2 μM) of , and their activity is comparable with standard drugs miltefosine and sodium stibogluconate. The most active compound was further studied against the/golden hamster model at a dose of 50 mg kg through the intraperitoneal route for 5 consecutive days, which displayed 75.04 ± 7.28% inhibition of splenic parasite burden. Pharmacokinetics of compound was studied in the golden Syrian hamster, and following a 50 mg kg oral dose, the compound was detected in hamster serum for up to 24 h. It exhibited a large volume of distribution (651.8 L kg), high clearance (43.2 L h kg) and long mean residence time (10 h).