Onychomycosis is associated with the cutaneous fungal infection of the nail and the nail folds (skin surrounding the nail). It is therefore important to target drug delivery into the nail folds along with nail plate and the nail bed. Systematic and strategic selection of the penetration enhancers specific for the skin and the nail is discussed. Twelve penetration enhancers were screened for their ability to improve solubility, in vitro nail penetration, in vitro skin permeation, and in vitro skin penetration of the antifungal drug ciclopirox olamine. In contrast to transdermal drug delivery, the main selection criteria for skin penetration enhancer in topical drug delivery were increased drug accumulation in the epidermis and minimal permeation across the skin. Thiourea improved the solubility and nail penetration of ciclopirox olamine. It also showed enhancement in the transungual diffusion of the drug. Propylene glycol showed a 12-fold increase in solubility and 3-fold increase in epidermal accumulation of ciclopirox olamine, while minimizing the transdermal movement of the drug. Thiourea was the selected nail permeation enhancer and propylene glycol was the selected skin penetration enhancer of ciclopirox olamine. A combination of the selected enhancers was also explored for its effect on drug delivery to the nail and nail folds. The enhancer combination reduced the penetration of ciclopirox in the skin and also the permeation through the nail. The proposed preformulation strategy helps to select appropriate enhancers for optimum topical delivery and paves way towards an efficient topical formulation for passive transungual drug delivery.

The study described herein was undertaken to simultaneously optimize the composition of tablet and capsule formulation of an insoluble experimental drug, and to learn more about the effect of the interaction between the ingredients on the basic properties of the final dosage form. Four independent variables were varied in a set of statistically designed experiments, and a number of properties evaluated. A substantial saving in development time and quantity of drug was thereby achieved.The techniques of optimization in pharmaceutical dosage form design are well d o c~m e n t e d ' *~*~?~. Schwartz et al? developed a technique whereby a formulation with optimum properties could be obtained through computer assisted data analysis. They used the results of a statistically designed series of experiments, based on five independent variables, as input into a computer. Down et al.7 used a desk top computer for product optimization. Their method offered rapid access and 2089 Copyright 0 1993 by Marcel Dekker, Inc. Drug Dev Ind Pharm Downloaded from informahealthcare.com by University of Otago on 01/03/15 For personal use only.