New approaches of identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms

Abstract

Tioconazole, a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses. The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the on line quality control and continuous process monitoring of tioconzole in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal (differential scanning calorimetry (DSC), melting point, and thermogravimetry(TG)), spectroscopic (ultraviolet (UV), RAMAN, near infrared (NIR), infrared spectroscopy coupled to attenuated total reflectance (FTIR-ATR), and nuclear magnetic resonance (NMR)), microscopic and X-ray diffraction (XRD). The tioconzole bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution (3?95 μm) resolved by microscopic measurements. Tioconazole melting point (82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of tioconazole was obtained by mono- and two- dimensional 1H and 13C NMR spectral data analysis. The FTIR-ATR, RAMAN and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for tioconazole identification in ovules were DSC, TG, XRD, NIR and RAMAN, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, RAMAN, FTIR-ATR and NIR spectroscopy are effective techniques to be used in on-line process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.