Elimination of fluconazole during continuous renal replacement therapy. An in vitro assessment (original) (raw)
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Journal of Artificial Organs
The aim of this study was to assess the adsorption of selected antibiotics: vancomycin, gentamicin, ciprofloxacine and tigecycline in an experimental continuous veno-venous hemofiltration circuit with the use of both polyethyleneimine-treated polyacrylonitrile (PAN) and the polysulfone (PS) filter membranes. The crystalloid fluid dosed with one of antibiotic was pumped from a reservoir through a hemofiltration circuit (with PAN or PS membrane) and back to reservoir. All ultrafiltrate was also returned to the reservoir. During the procedures samples were collected from the post-hemofilter port at 5, 15, 30, 45, 60, 90, and 120 min. To determine spontaneous degradation of the antimicrobials, an additional bag with each study drug was prepared, which was not attached to the hemofiltration circuit. The samples from these bags were used as controls. In the case of vancomycin, gentamycin and tigecycline there was a statistically significant decrease in the drug concentration in the hemofi...
Journal of Artificial Organs
The aim of this study was to assess the in vitro adsorption of antibiotics: vancomycin, gentamicin, ciprofloxacin and tigecycline on both polyethyleneimine-treated polyacrylonitrile membrane of AN69ST filter and polysulfone membrane of AV1000 filter using porcine blood as a model close to in vivo conditions. The porcine blood with antibiotic dissolved in it was pumped into hemofiltration circuit (with AN69ST or AV1000 filter), ultrafiltration fluid was continuously returned to the reservoir containing blood with antibiotic. Blood samples to determine antibiotic concentrations were taken at minutes 0, 5, 15, 30, 45, 60, 90 and 120 from the pre- blood pump of the hemofiltration circuit. To assess possible spontaneous degradation of the drug in the solution there was an additional reservoir prepared for each antibiotic, containing blood with the drug, which was not connected to the circuit. In the case of vancomycin, ciprofloxacine and tigecycline, a statistically significant decrease ...
Detection of Impurities in Bulk Drug and Capsule of Fluconazole
Asian Journal of Pharmaceutical Research and Development
Objectives: The purpose of this study was to identify the impurities and their amounts in the fluconazole bulk drug and capsule FLUNACTM (150 mg). Method: HPLC with diode array detector was used to carry out the study. The composition of mobile phase was acetonitrile: water (85:15 %) with flow rate of 0.7 mL/min and detected at 260 ± 1 nm. Results: Two impurities (one is known impurity A and other unknown impurity) were detected in the bulk drug and also in capsule FLUNAC (150mg). The total amount of impurities in fluconazole bulk drug and capsule were 0.368% and 0.392% respectively. Conclusion: The total amount of impurities was less than 1% which is acceptable.
Journal of Pharmaceutical and Biomedical Analysis, 2002
High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood. This technique requires careful sample preparation. Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability. Moreover, to obtain sufficient material for analysis, at least 1 ml of plasma is required. This constraint makes it difficult to determine drug levels when blood sample volumes are limited. However, drugs with low plasma-protein binding can be reliably extracted from plasma by ultra-filtration with a minimal loss due to the protein-bound fraction. This study validated a single-step ultra-filtration method for extracting fluconazole (FLC), a first-line antifungal agent with a weak plasma-protein binding, from plasma to determine its concentration by HPLC. Spiked FLC standards and unknowns were prepared in human and rat plasma. Samples (240 ml) were transferred into disposable microtube filtration units containing cellulose or polysulfone filters with a 5 kDa cut-off. After centrifugation for 60 min at 15000g, FLC concentrations were measured by direct injection of the filtrate into the HPLC. Using cellulose filters, low molecular weight proteins were eluted early in the chromatogram and well separated from FLC that eluted at 8.40 min as a sharp single peak. In contrast, with polysulfone filters several additional peaks interfering with the FLC peak were observed. Moreover, the FLC recovery using cellulose filters compared to polysulfone filters was higher and had a better reproducibility. Cellulose filters were therefore used for the subsequent validation procedure. The quantification limit was 0.195 mg l − 1 . Standard curves with a quadratic regression coefficient E 0.9999 were obtained in the concentration range of 0.195-100 mg l − 1 . The inter and intra-run accuracies and precisions over the clinically relevant concentration range, 1.875-60 mg l − 1 , fell well within the 9 15% variation recommended by the current guidelines for the validation of analytical methods. Furthermore, no analytical interference was observed with commonly used antibiotics, antifungals, antivirals and immunosuppressive agents. Ultra-filtration of plasma with cellulose filters permits the extraction of FLC from small volumes (240 ml). The determination of FLC concentrations by HPLC after this single-step procedure is selective, precise and accurate.
Physicochemical Compatibility and Stability of Reconstituted Fluconazole in Mini-Containers
2018
DOI: 10.21276/sajp.2018.7.1.7 Abstract: Multiple Intravenous drug administered in one route cannot be avoided in critical care as the need for various drug is higher than the amount of venous access, therefore this study is aimed at assessing the physicochemical compatibility and stability of fluconazole in infusion fluids over time. Two different brands of fluconazole infusion were reconstituted with Ringer‟s lactate solution (400 μg/mL), 5% Dextrose water (400 μg/mL) or Sodium bicarbonate injection (2mg/mL) in a separate polyvinyl chloride containers. The reconstituted samples were visually inspected for colour, odour changes, presence of particulate matter, and then assayed using a UV-Visible Spectrophotometric method in triplicate at time 0, 0.5, 1, 2, 8, and 24 hrs. The pH was further monitored at predetermined time interval. The reconstituted samples showed no colour or odour change and no particulate matter. The concentration of un-degraded fluconazole in the reconstituted sa...
A Comparative Validation Study of Fluconazole by HPLC and UPLC with Forced Degradation Study
Chromatography Research International, 2013
The simplest stability indicating reversed phase Isocratic HPLC and UPLC methods has been developed and validated for the determination of fluconazole in bulk and solid pharmaceutical dosage form. A SunFire C18 (250 × 4.5 mm, 5 μm particle size) column has been used for HPLC and BEH C18 (100 × 2.1 mm, 1.7 μm particle size) column used for UPLC. The Mobile phase consisted of Methanol : Water (70 : 30) for HPLC and Methanol : Water (55 : 45 v/v) for UPLC. Isocratic flow was set at 1 mL/min and 0.30 mL/min, respectively, for HPLC and UPLC. For both HPLC and UPLC system detection has been performed at 211 nm with 30°C column oven temperature (good elution was obtained at 30°C) and injection volume, respectively, 2 μL and 20 μL for HPLC and UPLC.
Dissolution Method Devolopment of Fluconazole in Fluconazole Tablets Dossage Form
The present research work discusses the development of a dissolution method for Fluconazole using UV spectrophotometer. Simple, accurate and cost efficient dissolution method has been developed for the estimation of Fluconazole in bulk and tablet dosage form. The optimum conditions for the dissolution of the drug were established. The dissolution media was found to be 0.1N HCl (pH 1.2). The apparatus was found to be USP II, Paddle and the speed was found to be 50 rpm for 30 minutes time interval.
A simple TLC method for analysis of fluconazole in pharmaceutical dosage forms
JPC - Journal of Planar Chromatography - Modern TLC, 2008
Use of an internal standard is proposed in this thin-layer chromatographic determination of fluconazole in tablet and capsule formulations. Determination of drugs in commercial formulations requires dilution, which is a serious source of analytical errors. It is known that an internal standard, if properly chosen, can help to eliminate this type of problem. This method, which was established and validated using clotrimazole as internal standard, is based on HPTLC separation of the two compounds on silica gel 60 GF 254 , with toluene-chloroform-methanol 1.2:3.0:0.4 (v/v) as mobile phase, followed by densitometric measurement of the spots at 210 nm. The retention factors for fluconazole and clotrimazole were 0.25 ± 0.024 and 0.62 ± 0.022 respectively. The response to fluconazole, either peak height and peak area, was a linear function of amount in the range 0.6-1.6 μg per band, with a constant amount of the IS. The method was validated for accuracy, precision, specificity, and linearity. Results from tablet and capsule assay had low coefficients of variation and the standard deviation was less than ±2. This indicates the accuracy and precision of the method are satisfactory. Excipients in both formulations did not interfere with determination of the drug.
Improvement of fluconazole flowability and its effect on dissolution from tablets and capsules
Brazilian Journal of Pharmaceutical Sciences, 2010
The aim of this work was to improve fluconazole flowability by wet granulation and to study the effect of granulation on drug dissolution from tablets and capsules. Fluconazole was submitted to a process of wet granulation in a high-speed granulator using Plasdone Ò K29/32 or K90. Flow properties of granules and dissolution profiles for tablets and capsules produced with them were determined. Fluconazole granules demonstrated better flowability, calculated by angle of repose and compressibility index data, compared with powder. Additionally, it was observed that the granulation process improved the dissolution efficiency (ED) of fluconazole from tablets and capsules, which could also suggest an increase in bioavailability. Higher dissolution efficiencies were achieved with Plasdone ® K29/32.