Development and evaluation of microemulsion formulations with tolnaftate

Microemulsions are considered as potential systems for poorly water soluble drugs delivery because of their ability to improve both lipophilic and hydrophilic drug solubilization, thermodynamic stability and ease of preparation. The aim of the present work was to formulate microemulsions containing poorly water soluble, topicaly used antifungal drug tolnaftate (O-2-naphthyl methyl (3-methylphenyl) thiocarbamate) and evaluate their biopharmaceutical characteristics. Experimental: Tolnaftate solubility in isopropyl myristate and Labrasol® were evaluated by high performance liquid chromatography method. 1 % tolnaftate solubility capacity was evaluated in 14 experimental formulations, containing following excipients: Labrasol®, Plurol isostearique®, Tween® 20, Tween® 80, PEG 400, 96.3º ethanol, isopropyl myristate, ethyl oleate, bidistilled water and formulations were analyzed microscopically and by Raman spectroscopy. Pseudo ternary phase diagrams for tolnaftate microemulsion region were constructed at surfactant to cosurfactant (S/CoS) ratios 5:1, 3:1, and 2:1. Different compositions of tolnaftate microemulsions were formulated using isopropyl myristate, Labrasol®, Plurol isostearique® with S/CoS ratios (5:1, 3:1, 2:1) and varying water content. Particle size was measured by dynamic light scattering method. Formulations with small droplet sizes and narrow range of particle size distribution were selected; tolnaftate release through dialysis membrane was performed. Results and conclusions: it was impossible to produce 1 % tolnaftate microemulsion from Labrasol®, Plurol isostearique®, Tween® 20, Tween® 80, PEG 400, 96,3º ethanol, isopropyl myristate, ethyl oleate, distilled water, in all samples crystallization occurred. Raman spectroscopy showed that crystals were formed from tolnaftate. According to the pseudo ternary phase diagrams S/CoS ratio increase was followed by microemulsion formation region plot decrease and lower ability to incorporate high water concentrations, however with increasing S/CoS ratio more homogeneous microemulsions were formed. In particle size measurements of selected formulations the mean diameter of microemulsion droplets was in range of 39 nm up to 252 nm. Tolnaftate release from these microemulsions was highest from samples with smaller particle size and higher water content