Electron Capture Gas Chromatographic Assay for Miconazole and Clotrimazole In Skin Samples

Abstract

Electron capture gas chromatographic assay procedures were developed for quantitating the antifungal agents clotrimazole and miconazole. The procedures were specifically developed for analysis of the drugs in superficial samples of human skin. The analytical methods were sensitive to 5 ng of miconazole and 10 ng clotrimazole per tissue sample.     

HPLC‐DAD for the determination of three different classes of antifungals: method characterization,statistical approach,and application to a permeation study

This study describes and characterizes methods for high‐performance liquid chromatography diode array detection (HPLC‐DAD) analysis of formulations containing molecules with antifungal activity of three different classes: terbinafine and butenafine (allylamines), miconazole and fluconazole (azoles), and geraniol, neral and geranial (monoterpenes). All methods used the same chromatographic column (RP₁₈), enabling the analysis to be performed in a single batch. The specificity was extensively discussed through the establishment of purity peak methods. The analytical parameters (linearity, precision and accuracy) were calculated and discussed in detail using specific statistical approaches. All substances showed satisfactory results for chromatographic and analytical parameters. Limits of 1.3% to mean repeatability and 2.0% for intermediate precision are suggested as acceptance criteria in validation of methods by HPLC‐DAD, in situations where there is no extensive pretreatment of the samples. The methods proved to be robust and significant factors were discussed regarding their influence on chromatographic parameters (retention time, resolution, tailing factor and column efficiency). Finally, the application of the developed methods was demonstrated by the results of a permeation study of the antifungal agents through bovine hoof membranes. Copyright © 2014 John Wiley & Sons, Ltd.     

毛细管电泳法测定复方制剂中的硝酸咪康唑

毛细管电泳;高频电导检测;非接触式电导检测;硝酸咪康唑;复方制剂     

Poloxamer-Stabilized Topical Miconazole Nitrate-Loaded Microemulsion: Formulation Design and Characterization

Miconazole nitrate-loaded microemulsion based on Tween 80 and propylene glycol, castor oil and water with and without Poloxamer 407 was prepared and characterized with respect to drug content, stability, antifungal, and physicochemical properties and ex vivo drug release using a modified Franz diffusion apparatus. Results obtained revealed homogeneous and stable microemulsions with excellent physicochemical properties, permeation coefficients and fluxes, and increased in vitro antifungal activity (～1.2 times) against clinically isolated Candida albicans when compared to a commercial topical miconazole (Fungusol) solution. Poloxamer-stabilized microemulsion could offer a better and more reliable approach of delivering miconazole than both the unstabilized and Fungusol formulations.      

Application of Supercritical Carbon Dioxide for the Preparation of Drug-Cyclodextrin Inclusion Compounds

Inclusion complexes of drugs into cyclodextrins (CDs) can be obtained at the solid state by means of supercritical dioxide (SCCO₂). A successful inclusion with a yield >98.5% has been achieved with piroxicam and -CD. The temperature and the time of exposure to SCCO₂ have a significant effect on the inclusion yield while the pressure has a negative effect. However, there is a strong interaction between temperature and pressure and this interaction has a positive influence. The molar ratio piroxicam--CD and the addition of ternary alkaline agents were also found to be significant factors. The dissolution rate of the complexes formed using SCCO₂ was found to be significantly higher than that of the physical mixture. Inclusion complexes have also been obtained with miconazole treating mixtures of miconazole, CDs and citric acid by SCCO₂. This new technique of inclusion of poorly soluble drugs into CDs allows the preparation of solid complexes without using organic solvents and thus without residues.     

Thermal analysis in evaluation of the radiochemical stability of some fungicidal drugs

Four azole derivatives showing antimycotic activity (Miconazole, Ketoconazole, Clotrimazole, Fluconazole) in solid phase were exposed to beta irradiation at the dose of 20-200 kGy and then alterations in the physicochemical properties of the above derivatives were studied using the methods: scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. It was found that the compounds irradiated with sterilising doses (20-50 kGy) showed no significant alterations in their physicochemical properties, while application of doses >50 kGy resulted in small changes in the X-ray diffraction patterns and in the course of DSC curves, including a decrease in the melting points and enthalpy of the process. For Miconazole and Fluconazole, a linear and relatively strong correlation was found (from r =0.9782 to r =0.9003) between the size of the dose of irradiation and the decrease in the melting point and enthalpy value. This revised version was published online in July 2006 with corrections to the Cover Date.