Designing a Test for Nail Safety Evaluation to Select Nail-friendly Permeation Enhancers

Abstract

In the present investigation a novel, scientific, simple, and reliable nail safety screening test based on Fourier-transform infrared spectroscopy was developed for the screening of nail-friendly transungual drug permeation enhancers. In this test, nail clippings were treated with the permeation enhancer and their FTIR spectra were recorded and compared with FTIR spectrum of untreated nail clipping. With the help of three spectral parameters namely, peak purity index, peak intensity ratio, and peak-fitting analysis any type of structural alteration brought out by the permeation enhancer in the matrix of nail plate could be determined and nail safety could be readily assessed. The validity of the proposed method was established by studying the effect of eight different types of permeation enhancers, thioglycolic acid, salicylic acid, n-acetyl-l-cysteine, sodium sulfite, resorcinol, sodium hydroxide, oxalic acid, and hydroxypropyl-β-cyclodextrin on the nail clippings. It was observed that thioglycolic acid, salicylic acid, sodium sulfite, resorcinol, sodium hydroxide, oxalic acid, and n-acetyl-l-cysteine severely damaged the nail plate keratin as evidenced by the significantly altered values of peak purity index, peak intensity ratio, and peak-fitting analysis, whereas hydroxylpropyl-β-cyclodextrin was found to be innocuous as the above three spectral parameters remained almost unaltered. This technique could be easily employed for screening nail-friendly drug permeation enhancers from the large pool of available chemical permeation enhancers during the preformulation stage of development of transungual drug delivery systems.