Onychomycosis of the nail plate and nail bed affects about 5% of the population of industrial nations and 14% of the entire population. Onychomycosis is difficult to treat. Serious infections are treated chronically with systemic antimycotics; such as terbinafine and itraconazole, which expose the organism to a considerable amount of drug and result in significant adverse events. Therefore, an unmet medical need for safely treating onychomycosis exists and a topical therapeutic approach is essential. Since the introduction of the medicinal commercial nail lacquers (Penlac™ and Loceryl ®), topical treatment has become more and more popular for mild to intermediate mycoses; however, efficacy of these topical products have been inferior to the systemic treatment. Up to now the mechanism of transungual (through the nail) permeation is largely unknown. The release of drugs from medicinal nail lacquers and its modulation is not clearly understood. There are no relationship models that enable one to conveniently optimize formulation parameters in the drug release patterns. Assuming that transungual drug permeation follows a simple diffusion process through the nail plate and that the drug release from the nail lacquer film is a key factor for the efficacy of topically applied anti-mychomycotic drugs, this research project concentrated on drug (clotrimazole) release from a nail lacquer and studied how various formulation parameters can be modulated in order to achieve optimal drug delivery to the nail plate. The release profile data, more specifically the release rate constants of all the formulations were calculated and have been analyzed for statistically significant correlations with formulation parameters.
Similarly, the formulation characteristics (e.g., vehicle, drug concentration, formulation excipients, i.e., type of polymer) of the nail lacquer formulations may be best described by the adhesion properties of the films. The adhesion characteristics were measured for all the formulations and a key outcome, i.e., work of adhesion, was calculated and analyzed for any statistically significant correlation with formulation parameters.
Release profiles of clotrimazole were generated using an "in vitro release test" (IVRT) apparatus. Synthetic membranes were used as substrate. The adhesion characteristics were measured using a TA.XT2 i Texture Analyzer.
Finally, a statistical analysis was done to derive a correlation between drug release rate constants of the nail lacquer formulations and their adhesion characteristics (work of adhesion), wherein the formulation parameters of the drug/solvent/polymer product may determine the work of adhesion which in turn impacts the drug release rate constant. A semi-empirical mathematical formula was developed based on the correlation between the drug release rate constants and work of adhesion.
The study demonstrated that varying release and adhesive properties may be achieved by modulating the concentrations of drug, polymer and tailing solvent. Attempts were made to choose ideal polymer (Gantrez) and solvent (propylene glycol). Both the excipients give enough adhesion and plasticity respectively. Increase in concentrations of polymer or drug increased the release rate constants but not with propylene glycol. On the other hand, an increase in polymer concentration only increased adhesive properties (work of adhesion) but not with drug or propylene glycol. However, we found a correlation between adhesive properties and release rate constants of nail lacquers containing all three factors i.e. drug, polymer and propylene glycol at varying levels. Using the correlation equation, there may be a potential for predicting drug release rate constants from their adhesive properties. This could be beneficial to develop optimal formulations of medicinal nail lacquer dosage forms.