Danielle Vanbeckbergen

Long‐term stability of cefuroxime and cefazolin sodium in intravenous infusions

Cefazolin and cefuroxime sodium are often used as antibiotic infusions for hospitalized patients. Because advance preparation of these intravenous solutions is efficient, the stability of both antibiotics stored at 4 °C in polyvinyl chloride (PVC) bags was studied.

Effect of the freezing conditions and microwave thawing power on the stability of cefuroxime in dextrose 5% infusion polyolefin bags at 4 degrees C.

BACKGROUND Intravenous cefuroxime sodium solution could be prepared in advance by a centralized hospital pharmacy service to improve safety and time management. OBJECTIVE To investigate the effect of freezing and microwave thawing on the solution stability of cefuroxime. METHODS Cefuroxime 1.5 g in 100 mL of dextrose 5% in polyolefin bags was frozen individually (group A) or in one package (group B) for 98 days at −20 °C. The solutions were then thawed using microwaves at 270 (light cycle) or 800 watts (hard cycle) and stored at 4 °C. The cefuroxime concentration was measured by HPLC. Visual inspection was performed and pH was measured at that time. Stability of the solution was defined as a concentration remaining superior to 90% of the initial concentration by regression analysis. RESULTS No color change or precipitation in the solutions was observed. In group A, stability was at least 23 and 21 days after light and hard cycle thawing, respectively. In group B, stability was at least 21 and 18 days, respectively, with the pH increasing without affecting chromatographic parameters. CONCLUSIONS The optimal conditions for advance preparation of a solution containing cefuroxime 1.5% in dextrose 5% may be freezing of individual containers followed by a light cycle of microwave thawing.

Doxorubicin-loaded drug-eluting beads (DC Bead®) for use in transarterial chemoembolization: A stability assessment

Purpose: Evaluation of doxorubicin stability over time when stored into the DC Bead embolic agent, in various containers, which are used for the delivery of the doxorubicin-loaded beads to the patients for up to 14 days under refrigerated conditions. Methods: The doxorubicin was loaded through the ionic exchange mechanism into the calibrated polyvinyl alcohol-based hydrogel beads (DC Bead), with the loading process carried out either in the original DC Bead glass vials or within a polypropylene plastic syringe. The loaded samples were eluted at given time points and the extracted doxorubicin was analysed by high-performance liquid chromatography for concentration and chromatographic area response purity. Results: The variance on the doxorubicin concentration of the samples stored in the syringes under refrigerated conditions was less than 10% over the 14 days period. The chromatographic purity of doxorubicin eluted from the DC Bead in their primary glass vial packaging was measured at 99.7%. The dissolution test showed that the elution rate and amount recovered from samples stored in vials were statistically similar between Day 0 and Day 14. The chromatographic purity of the doxorubicin loaded into DC Bead in presence of non-ionic contrast medium was >99.0% for 7 days under refrigerated conditions. Conclusions: Doxorubicin-loaded DC Bead® are shown to have adequate physicochemical stability over a period of 14 days when stored in syringes or vials under refrigerated conditions for up to 14 days. The admixtures of doxorubicin-loaded beads with contrast medium are stable for up to 7 days under refrigerated conditions.

Effect of Freezing, Long-Term Storage, and Microwave Thawing on the Stability of Ketorolac Tromethamine

BACKGROUND: Ketorolac tromethamine is a nonsteroidal agent with potent analgesic and moderate antiinflammatory activity. Advance preparation of intravenous solution could be useful to improve quality assurance, time management, and cost-savings of drug delivery. Objective: To investigate the effect of freezing, long-term storage, and microwave thawing on the stability of ketorolac tromethamine in dextrose 5% infusion. METHODS: Five polyolefin bags of solution containing ketorolac tromethamine 20 mg per 100 mL of dextrose 5% were frozen for 3 months at −20 °C, thawed in a microwave oven with a validated cycle, and stored at 4 °C. The concentration of ketorolac was measured by HPLC. Visual inspection and pH measurement were also carried out. RESULTS: No color change or precipitation was observed. Ketorolac was stable for at least 60 days under refrigeration after freeze–thaw. Throughout this period, the lower confidence limit of the estimated regression line of the concentration–time profile remained >90% of the initial concentration, and the pH value decreased slightly without affecting chromatographic parameters. CONCLUSIONS: Within these limits, ketorolac tromethamine in dextrose 5% infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.

Long-term stability of vancomycin hydrochloride in intravenous infusions.

Background and objective: Vancomycin is often used in antibiotic infusions for hospitalized patients and it is advantageous to prepare such intravenous solutions in advance. The objective of this study was to investigate the long‐term stability of this antibiotic stored at 4 d̀C in polyvinyl chloride (PVC) bags.

Effect of freeze-thawing on the long-term stability of calcium levofolinate in 5% dextrose stored on polyolefin infusion bags.

Background:  Calcium levofolinate infusions could be prepared in advance by a centralized intravenous additive service (CIVAS) to improve safety and time management.

Particle counting immunoassay for urinary cotinine. Comparison with chromatography, enzyme-linked immunoassay and fluorescence polarization immunoassay.

Abstract Urinary cotinine was measured according to its inhibitory activity on the agglutination of cotinine-coated latex particles by anti-cotinine antibodies, the agglutination being measured by optical counting of the remaining non-agglutinated particles (particle counting, PaC). The detection limit was 0.03 μg/ml and the practical range extended from 0.03 to 3.9 μg/ml. The correlation results of 320 urine samples with those of high pressure liquid chromatography, enzyme-linked (Coti-Tracq EIA, Serex Inc., Maywood, NJ, USA), and fluorescence polarization immunoassay (TDX instrument, Abbott, Abbott Park, IL, USA) were r = 0.90, r = 0.69, r = 0.87, respectively, whereas the correlation coefficients between the assays other than particle counting ranged from 0.62 to 0.88. PaC does not require any separation step and can thus be easily automated.

Stability of Ondansetron and Dexamethasone Infusion upon Refrigeration

Ondansetron is a serotonin receptor antagonist used in the treatment of chemotherapy-induced emesis1; the addition of dexamethasone increases the antiemetic efficacy.2 Advance preparation of intravenous solutions by a centralized intravenous additive service might improve quality assurance.3 Two studies have reported the stability of ondansetron stored at −20 °C.4,5 Our study investigated the stability of the combination of ondansetron hydrochloride plus dexamethasone sodium phosphate in dextrose 5% in polyolefin bags after freezing, microwave thawing, and long-term storage at 5 ± 3 °C.

Physico-chemical analysis of several injectable drug in ready-to-use infusion after microwave freeze-thaw treatment and final storage at 5 ± 3 ◦ C

OBJECTIVE In hospitals, the majority of the reconstitution of injectable drugs are carried out right before the administration to the patient by the nursing staff. The risks and errors related on their preparation and administration are numerous. The standardization, the centralization of these preparations and reconstitution by the hospital pharmacy make it possible to reduce the various risks and errors To enhance the number of drugs taken in charge, it is necessary to develop the long-term stability of ready-to-use drugs. Freezing seems an easy method but defrosting takes too much time. Some authors develop the concept of microwave treatment and apply this to different drugs. A characteristic of these studies was nevertheless the short period of study after thawing. METHODS Long-term stability studies were started for different drugs mainly used in the hospital, and verify their stability after freezing at temperature<- 25°C, long-term storage (1 to 4 months), microwave-thawing and long-term storage at 5 ± 3°C. RESULTS Sixteen molecules were tested and preserve more than 90% of their initial concentration the day of defrosting by microwave oven like this value a certain number of days at 5 ± 3°C. All the analyses were carried out by HPLC. CONCLUSION The microwave freeze/thawing treatment allows the production of more important batches, makes profit of this technique in workload and material beyond a certain produced quantity. The described results encourage to check the possibilities of taking in charge other molecules regularly used in the Hospital Institutions.

Long-term stability of tramadol hydrochloride and droperidol mixture in 5% dextrose infusion polyolefin bags at 5 ± 3 °C

OBJECTIVE To investigate the stability of tramadol hydrochloride 100mg associated with droperidol 2.5mg in 100ml of 5% dextrose solution stored at 5+/-3 degrees C. METHODS Solutions of 5% dextrose 100ml in polyolefin bags (n=5) containing approximately tramadol hydrochloride 100mg associated with droperidol 2.5mg were prepared under aseptic conditions and stored about 32 days at 5+/-3 degrees C. The tramadol hydrochloride and droperidol concentrations were measured by high performance liquid chromatography (HPLC). Visual inspection was performed and pH was measured periodically during the storage. Stability of the solutions was defined as the common regression line 95% lower confidence limit of the concentration remaining superior to 90% of the initial concentration as recommended by the Food and Drug Administration (FDA). RESULTS No colour change or precipitation in the solutions was observed. Tramadol hydrochloride 100mg associated with droperidol 2.5mg in 100 ml of 5% dextrose infusions was stable when stored at 5+/-3 degrees C during 32 days. Throughout this period, the lower confidence limit of the estimated regression line of concentration-time profile remained above 90% of the initial concentration. There was no significant change in pH during storage. CONCLUSION Under the conditions of this study, tramadol hydrochloride 100mg associated with droperidol 2.5mg in 100 ml of 5% dextrose infusions stored up to 32 days at 5+/-3 degrees C remain stable and may be prepared in advance by CIVAS to improve safety and management.