LC method for the analysis of Oxiconazole in pharmaceutical formulations.
A LC method has been developed for the quantitative determination of Oxiconazole (Ox) in bulk form, lotion and cream pharmaceutical formulations. The method validation yielded good results including the range, linearity, precision, accuracy, recovery, specificity, robustness, limit of quantitation and limit of detection. The LC separation was carried by reversed phase chromatography using a LiChrocart C(8) column (125 mm x 4.0 mm i.d., 5 microm particle size). The mobile phase was composed of methanol-0.02 M ammonium acetate buffer (85:15 v/v), pumped isocratically at flow rate 1 ml min(-1). The detection was carried out on UV detector at 254 nm. The calibration curve for Ox was linear from 40.0-140.0 microg ml(-1) range. The precision of this method, calculated as the relative standard deviation (R.S.D.) was 1.57% for lotion and 0.71% for cream. The R.S.D. values for intra- and inter-day precision studies were 0.57 and 1.34%, respectively. The recovery of the drug ranged between 98.84-102.2% (lotion) and 100.54-101.59% (cream). The stability indicating capability of the assays was proved using forced degradation. Chromatograms showed Ox well resolved from the degradation product.
Study of the forced degradation of isoconazole nitrate in bulk drug and cream formulations
Bulk drug and cream formulations of isoconazole were subjected to the following ICH-recommended stress conditions: hydrochloric acid (0.1 M), sodium hydroxide (0.1 and 1 M), and hydrogen peroxide (3%). Photostability was monitored for 60 h in a UV chamber. Analysis of drug degradation was performed using an HPLC method that had been validated for linearity, range, precision, accuracy, limits of detection and quantification, and selectivity and robustness in accordance with the criteria established by Resolution 899 of the Brazilian National Health Surveillance Agency (ANVISA). When isoconazole cream was exposed to a light source, the isoconazole content decreased slightly, but no degradation products were formed as indicated by the absence of additional peaks in the HPLC chromatogram. The drug was found to be unstable in both the bulk form and in the cream formulation when subjected to alkaline hydrolysis conditions, exhibiting reductions of ca. 43 and 70% of the initial content, respectively. Different sample solutions that had been subjected to alkaline degradation indicated, through subsequent pH adjustments and UV analysis, the presence of an isosbestic point at 275 nm, suggestive of a reversible phenomenon in alkaline media. Reversibility by bringing the pH back to the initial value may be a valuable tool for identifying real degradation processes. In contrast to the drug's instability under alkaline conditions, isoconazole was found to be stable under both acid hydrolysis and oxidative conditions.
Formation and antimycotic effect of cyclodextrin inclusion complexes of econazole and miconazole
The stability constants between β-cyclodextrin (β-CD) and the two antimycotic imidazole derivatives, miconazole and econazole were measured. Increased ionization of the imidazole derivatives decreased the size of the stability constants. The same phenomenon was observed for miconazole and hydroxypropyl-β-cyclodextrin. In addition, the type of solubility diagram obtained was dependent on the degree of ionization of the imidazole derivatives. A type Bs solubility diagram was obtained for econazole and β-CD in buffer solution, pH 7.1. An econazole β-CD complex with a molar ratio of 1:1 was isolated. In a fluid medium the antimycotic effect of the econazole β-CD complex against a strain of Candida albicans was superior to the effect of a physical mixture of the two compounds. A small inhibitory effect of β-CD on the growth of the test organism was observed.