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International Journal of Pharmaceutics Dec 2011Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and...
Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole.
Topics: Antifungal Agents; Calorimetry, Differential Scanning; Chromatography, High Pressure Liquid; Crystallization; Drug Stability; Maleates; Miconazole; Powder Diffraction; Solubility; Tandem Mass Spectrometry; X-Ray Diffraction
PubMed: 21983091
DOI: 10.1016/j.ijpharm.2011.09.034 -
Drug Development and Industrial Pharmacy Sep 2021Miconazole nitrate (MIC) and nystatin (NYS) combination has proven its effectiveness as a prodigious therapy to cure women's common infections; vaginal candidiasis and...
Miconazole nitrate (MIC) and nystatin (NYS) combination has proven its effectiveness as a prodigious therapy to cure women's common infections; vaginal candidiasis and vaginal mycosis. Herein, six smart UV-spectrophotometric platforms depending on minimal mathematical manipulation steps were first introduced for the simultaneous green analysis of MIC and NYS in their pure forms and commercial vaginal suppositories without any preliminary separation steps. These platforms included dual-wavelength, ratio difference, mean centering of ratio spectra, first derivative ratio, ratio subtraction, and absorption correction methods. All of the aforementioned platforms could estimate MIC in a linear range of 90-900 µg/ml. While NYS was computed directly by zero-order spectrophotometry at its (304 nm) in a linear range of 1-15 µg/ml without any interference by MIC even in low or high concentrations. Dual-wavelength and zero-order spectrophotometric platforms were successfully applied to study the dissolution profile of MIC and NYS in their combined formulation in compliance with FDA recommendations without excipients interference. According to ICH guidelines, all platforms were validated regarding the accuracy, precision, and selectivity producing satisfactory results within the accepted limits. Also, the suggested platforms' results were statistically compared with each other and with those of the reported HPLC platform revealing no significant difference concerning accuracy and precision at = .05. Accordingly, all proposed platforms are regarded as economic and eco-friendly alternatives to the expensive chromatographic platforms that utilize hazardous organic solvents during the analysis of cited drugs.
Topics: Female; Humans; Miconazole; Nystatin; Solubility; Spectrophotometry; Suppositories
PubMed: 34727001
DOI: 10.1080/03639045.2021.2001490 -
British Journal of Clinical Pharmacology Oct 2004The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
AIMS
The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day(-1)).
METHODS
A three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period.
RESULTS
In all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 micro g ml(-1) (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 microg ml(-1) (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10-14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 micro g ml(-1). Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets.
CONCLUSIONS
These data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.
Topics: Administration, Oral; Adult; Antifungal Agents; Cross-Over Studies; Delayed-Action Preparations; Female; Gels; Humans; Male; Miconazole; Plasma; Saliva; Tablets
PubMed: 15373926
DOI: 10.1111/j.1365-2125.2004.02154.x -
AAPS PharmSciTech 2009The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate....
The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.
Topics: Administration, Cutaneous; Antifungal Agents; Cadaver; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallography, X-Ray; Drug Carriers; Drug Compounding; Drug Stability; Fatty Acids; Gels; Glycerides; Humans; Kinetics; Miconazole; Nanoparticles; Particle Size; Polysorbates; Propylene Glycol; Skin; Skin Absorption; Solubility; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents; Technology, Pharmaceutical
PubMed: 19294517
DOI: 10.1208/s12249-009-9199-0 -
Clinical Pharmacology and Therapeutics Jun 1992Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the...
Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the oxidation of both (R)- and (S)-warfarin to phenolic metabolites, although (S)-warfarin was inhibited to the greater extent. In particular, (S)-7-hydroxylation, the pathway primarily responsible for termination of the anticoagulant effect, was most strongly inhibited. Inhibition of warfarin hydroxylation by miconazole in human liver microsomes and the in vivo results showed a good rank order correlation. The enhanced anticoagulant effect observed when miconazole and warfarin are coadministered may result from inhibition of P4502C9, the isozyme of P450 primarily responsible for the conversion of (S)-warfarin to (S)-7-hydroxy-warfarin. Because miconazole inhibits a number of P450 isozymes, in addition to P4502C9, it can be expected to lead to interactions with other drugs whose primary metabolism is controlled by these enzymes.
Topics: Adult; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Female; Half-Life; Humans; Hydroxylation; Kinetics; Male; Miconazole; Microsomes, Liver; Mixed Function Oxygenases; Prothrombin Time; Stereoisomerism; Warfarin
PubMed: 1611805
DOI: 10.1038/clpt.1992.78 -
Analytical and Bioanalytical Chemistry Nov 2017Miconazole has one chiral center, and consists of two enantiomers. In this study, a novel chiral liquid chromatography-tandem mass spectrometry method was developed for...
Miconazole has one chiral center, and consists of two enantiomers. In this study, a novel chiral liquid chromatography-tandem mass spectrometry method was developed for enantioselective separation and determination of miconazole in rat plasma. For the first time, the enantioselective pharmacokinetics of miconazole was investigated by the current method. Firstly, attempts were made to separate the enantiomers in reversed-phase mode with a mobile phase that was mass spectrometry compatible. Baseline separation was achieved on a Chiralpak IC column with a mobile phase composed of acetonitrile and aqueous ammonium hydrogen carbonate (5 mM; 80:20, v/v). Data were acquired in multiple reaction monitoring mode with positive electrospray ionization by triple-quadrupole mass spectrometry. Then, overall method validation regarding the linearity, accuracy, precision, extraction recovery, matrix effect, and stability of each enantiomer was performed, and acceptable results were obtained for all of these. Finally, the method developed was applied in an enantioselective pharmacokinetic study of miconazole enantiomers in rats after oral administration of racemic miconazole at doses of 5 and 10 mg/kg. The results demonstrated that (-)-(R)-miconazole had a higher concentration than (+)-(S)-miconazole in plasma, with a ratio of 1.3-1.7 for both doses. This is the first experimental evidence of enantioselective behavior of miconazole in vivo, and provides a reference for clinical practice and encourages further research into miconazole enantioselective metabolism and drug interactions. Graphical Abstract A stereoselective pharmacokinetic study of the miconazole enantiomers was investigated using a novel chiral liquid chromatography-tandem mass spectrometry method. Baseline separation was achieved on Chiralpak IC column, and Chiralcel OJ column was used to collect single enantiomer. A significant difference between the two enantiomers was observed in view of the plasma concentration.
Topics: Administration, Oral; Animals; Antifungal Agents; Chromatography, High Pressure Liquid; Miconazole; Rats; Rats, Wistar; Stereoisomerism; Tandem Mass Spectrometry
PubMed: 28852798
DOI: 10.1007/s00216-017-0551-z -
Journal of Chromatographic Science Jan 2020Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance...
A Validated Ultra-Performance Liquid Chromatographic Method for the Simultaneous Determination of Nadifloxacin, Mometasone Furoate and Miconazole Nitrate in Their Combined Dosage Form and Spiked Human Plasma Samples.
Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance liquid chromatographic method coupled with a diode array detector (RP-UPLC-DAD) was developed and validated to determine nadifloxacin, mometasone furoate and miconazole nitrate simultaneously in their bulk powder, in pharmaceutical preparation and in spiked human plasma samples. Separation was achieved on an ACQUITY UPLC C18 column of 2.2 μm particle size (2.1 × 100 mm) via isocratic elution using a mobile phase consisting of methanol, acetonitrile and water with ratio (50:20:30; v/v/v) and 0.1 g ammonium acetate, then pH was adjusted to (7.00) using acetic acid, flow rate 0.6 mL/min, temperature 30°C and UV detection at 220 nm. The method is linear in a range from 5 to 400 μg/mL for both nadifloxacin and miconazole nitrate and from 20 to 500 μg/mL for mometasone furoate. The method was validated according to the ICH guidelines then applied successfully to determine the mentioned drugs in their pharmaceutical preparation and spiked human plasma samples. For plasma samples, the results showed that the method can determine nadifloxacin, mometasone furoate and miconazole nitrate in human plasma samples with high accuracy and precision.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Fluoroquinolones; Humans; Limit of Detection; Linear Models; Miconazole; Mometasone Furoate; Quinolizines; Reproducibility of Results
PubMed: 31602483
DOI: 10.1093/chromsci/bmz082 -
Clinical and Experimental Dermatology Dec 1979
Comparative Study
Topics: Administration, Topical; Benzoates; Corynebacterium Infections; Drug Combinations; Erythrasma; Female; Humans; Imidazoles; Male; Miconazole; Salicylates; Skin Diseases, Infectious
PubMed: 535173
DOI: 10.1111/j.1365-2230.1979.tb01640.x -
Pharmaceutical Biology Feb 2015Miconazole (MIZ) and econazole (ECZ) are clinically used as antifungal drugs. (Comparative Study)
Comparative Study
CONTEXT
Miconazole (MIZ) and econazole (ECZ) are clinically used as antifungal drugs.
OBJECTIVE
The drug effect and binding property with transport protein human serum albumin of MIZ and ECZ were studied.
MATERIALS AND METHODS
The antifungal efficiency was investigated by microdiluting drug solutions from 0 to 48 μmol L(-1) through microcalorimetry and voltammetry studies. Transmission electron microscopy was used for morphological observations of C. albicans. The interaction with HSA was studied by electrochemical methods, fluorescence spectrometry, electron microscopy, and molecular simulation.
RESULTS
IC50 of MIZ and ECZ for C. albicans were obtained as 19.72 and 29.90 μmol L(-1). Binding constants of MIZ and ECZ with HSA of 2.36 × 10(4) L mol(-1) and 3.73 × 10(4) L mol(-1) were obtained. After adding MIZ solution of 12 and 40 μmol L(-1), the peak currents increased to 4.887 and 6.024 μA. The peak currents of C. albicans in the presence of 20 and 48 μmol L(-1) ECZ were 4.701 and 5.544 μA. The docking scores for MIZ and ECZ of the best binding conformation in site I and site II were 5.60, 4.79, 5.63, and 5.85.
DISCUSSION AND CONCLUSION
Strong inhibition to the metabolism of C. albicans and destructive effect was proved for both drugs. The lower IC50, growth rate constant of C. albicans, and higher peak current, reveal stronger antifungal activity of MIZ. Both drugs show an efficient quenching effect to intrinsic fluorescence residues of protein. MIZ mainly binds on site I while ECZ on site II. Molecular modeling experiments give further insight of the binding mechanism.
Topics: Antifungal Agents; Candida albicans; Carrier Proteins; Dose-Response Relationship, Drug; Econazole; Humans; Miconazole; Microscopy, Electron, Transmission; Molecular Docking Simulation; Protein Binding; Serum Albumin; Spectrometry, Fluorescence
PubMed: 25376919
DOI: 10.3109/13880209.2014.914232 -
Journal of Pharmaceutical and... 1989Methods based on derivative UV spectrophotometry and high-performance liquid chromatography (HPLC) have been developed for the selective determination of miconazole and...
Methods based on derivative UV spectrophotometry and high-performance liquid chromatography (HPLC) have been developed for the selective determination of miconazole and econazole in pharmaceutical dosage forms. A solid-phase extraction (SPE) procedure using a diol column gave quantitative drug extraction from formulated creams and provided purified sample solutions suitable for assay by the derivative UV spectrophotometric and HPLC methods. The proposed methods gave comparable accurate results, whereas a conventional UV spectrophotometric method was found to be seriously affected by excipients.
Topics: Chromatography, High Pressure Liquid; Econazole; Indicators and Reagents; Miconazole; Ointments; Powders; Spectrophotometry, Ultraviolet
PubMed: 2490540
DOI: 10.1016/0731-7085(89)80162-1