Search

In order to avoid fluid overload, more concentrated drug solutions in intensive care units are commonly used. This study evaluated the physicochemical stability of concentrated solution of isosorbide dinitrate in polypropylene syringes during 28 days at 5°C ± 3°C with protection from light. Five syringes of 50 mL, containing 0.60 mg/mL of isosorbide dinitrate in sodium chloride 0.9% were prepared and stored at 5°C ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, isosorbide dinitrate concentration was measured by an ultra-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurements, and microscopic observations were also performed. All solutions were physicochemically stable during the whole period storage at 5°C ± 3°C. No color change, turbidity, precipitation or opacity, significant pH variations, or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. The concentration of isosorbide dinitrate remained above 90% of the initial concentration during the 28 days of storage. Solutions of isosorbide dinitrate 0.60 mg/mL in syringe of sodium chloride 0.9 % injection can be considered physically and chemically stable for 28 days when stored in syringes at 5°C ± 3°C with protection from light and may be prepared in advance by a centralized intravenous additive service., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

In some emergency clinical situations, the injection of a more concentrated drug solution in the intensive care units is common. The purpose of this study was to evaluate the physicochemical stability of concentrated solutions of amiodarone hydrochloride in polypropylene syringes during 28 days of storage at 5°C ± 3°C, with protection from light. Five syringes of 50 mL, containing 25 mg/mL of amiodarone in dextrose 5%, were prepared and stored at 5°C ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, amiodarone hydrochloride concentrations were measured by ultra-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. All solutions were physicochemically stable during the study period when stored at 5°C ± 3°C. No color change, turbidity, precipitation, opacity, significant pH variations, or optic densities were observed in the solutions. No crystals were seen by microscopic analysis. The concentration of amiodarone did not decrease during the 28 days of storage. Solutions of amiodarone 25 mg/mL in syringes of dextrose 5% are physically and chemically stable for at least 28 days when stored in syringes at 5°C ± 3°C with protection from light and may be prepared in advanced by a centralized intravenous additive service., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Intensive care units use drug solutions within higher concentrations to avoid fluid overload. The purpose of this study was to evaluate the physicochemical stability of concentrated solutions of noradrenaline bitartrate in polypropylene syringes during 30 days of storage at 5°C ± 3°C. Five 50-mL syringes containing 0.240 mg/mL of noradrenaline bitartrate in 0.9% sodium chloride were prepared and stored at 5°C ± 3°C during 30 days. Immediately after preparation and periodically during the storage, noradrenaline concentrations were measured by high-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. The results showed that all solutions were physicochemically stable during the entire storage period at 5°C ± 3°C, and no color change, turbidity, precipitation, opacity, significant pH variations, nor optic densities were observed. Microscopic analysis was used to determine if there was any formation of crystals. The concentration of noradrenaline was not found to decrease during the 30 days of storage. Solutions of noradrenaline bitartrate 0.240 mg/mL in syringes of 0.9% sodium chloride were physically and chemically stable for at least 30 days when stored in syringes at 5°C ± 3°C and may be prepared in advanced by a centralized intravenous additive service., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

The objectives of this study were to determine if the preparation of vancomycin hydrochloride in advance of infusion could improve the quality of the drug, time management of drug delivery, cost savings of drug delivery, and to investigate the long-term stability of vancomycin hydrochloride (brand name Vancocin®) infusion in glucose 5% polyolefin bags versus the generic (Vancomycine®) at 5°C ± 3°C. Five bags of each infusion 1 g/100 mL vancomycin hydrochloride in 5% glucose (Vancocin ® and Vancomycine®) were stored up to 57 days at 5°C ± 3°C. A visual inspection and pH measurement were performed periodically during the storage, and the concentrations were measured by high-performance liquid chromatography-diode array detection. No color change or precipitation in the solution was observed throughout the study period. As recommended by the U.S. Food and Drug Administration, the lower confidence limit at 95% of the concentration for the solutions remained superior to 90% of the initial concentration up to 43 days for the brand vancomycin (Vancocin®) infusion (96% ± 2%) and up to 57 days for the generic (Vancomycine®) (95% ± 4%). The solutions prepared either from brand or generic vancomycin hydrochloride were chemically stable more than one month (43 days for the brand and 57 days for the generic solution) and could be prepared in advance in a centralized intravenous additive service facility., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Vancomycin hydrochloride is often used for antibiotherapy in oral solution for hospitalized patients. Preparation of this solution in advance could improve time management or cost savings of drug delivery. Brand and generic products of vancomycin hydrochloride are now commercially available. The aim of this study was to investigate the long-term stability of the vancomycin hydrochloride brand name Vancocin versus the generic Vancomycine at 5°C ± 3°C. Five vials of each oral solution of 1.25 g/100 mL Vancocin and Vancomycine were stored up to 57 days at 5°C ± 3°C. Concentrations were measured by high-performance liquid chromatography-diode array detection. Visual inspection by microscopy and spectrophotometry, as well as pH measurement, were performed periodically during the storage period. No color change or precipitation in the solution was observed throughout the study period. The lower confidence limit of the concentration for these solutions remained superior to 90% of the initial concentration as recommended by the U.S. Food and Drug Administration up to a 57-day storage period for Vancocin (106.47%) and vancomycin (102.73%). The solutions prepared either from brand or generic vancomycin hydrochloride were chemically stable for more than one month and could be prepared in advance., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

To improve quality assurance, security, time management, and cost saving of drug delivery, preparation in advance of intravenous solutions has been developed for several infusion solutions. The objective of this study was to investigate the stability of esomeprazole 0.4 mg/mL and 0.8 mg/mL in 5% dextrose polyolefin bags after freezing, long-term storage, and microwave thawing. The stability of five polyolefin bags containing approximately 0.4 mg/mL of esomeprazole and five other bags containing approximately 0.8 mg/mL in 5% dextrose prepared under aseptic conditions was studied after freezing for 1 month at -20 degrees C, thawing in a microwave oven with a validated cycle, and stored at 5 degrees C +/- 3 degrees C. Esomeprazole concentration was measured by high-pressure liquid chromatography using a reversed-phase column C8, a mobile phase consisting of 35% of acetonitrile and 65% of Na2HPO4 buffer at pH 7.59 with HPO4 (2 M) and NaOH (0.5 M), and detection with a diode array detector at 280 nm. Visual, microscopic, and spectrophotometric observation and pH measurements were also performed. No precipitation occurred in the preparations but little change of color was observed. No microaggregate was observed with optical microscopy or revealed by a change of absorbance at 350, 410, and 550 nm. Based on a shelf life of 90% residual potency, esomeprazole solutions (0.4 and 0.8 mg/mL) were stable for at least 20 or 29 days, respectively, after a freezing and microwave thawing period, where 95% one-side lower confidence limit of the concentration-time profile remained superior to 90% of the initial concentration. During this period, the pH values of drug solutions have been observed to decrease without affecting chromatographic parameters. Within these limits, esomeprazole (0.4 and 0.8 mg/mL) in 5% dextrose infusions may be prepared and frozen in advance by a centralized intravenous admixture service, thawed, and stored at least 20 days at 5 degrees C +/- 3 degrees C before use in clinical units.

The objective of this study was to investigate the stability of cocaine hydrochloride 50 mg/mL (5%) aqueous solution stored in glass bottles at 5°C ± 3°C or at room temperature. Ten bottles of cocaine hydrochloride 50 mg/mL were prepared under aseptic conditions. Five were stored at 5°C ± 3°C and five at room temperature. pH measurements, optic density measurements at different wave-lengths, and optic microscopic observations were performed periodically during the storage. A forced-degradation test with hydrochloric acid 12M and NaOH 5M with and without heating at 100°C was also performed. The concentrations were measured by high-pressure liquid chromatography with photodiode-array detection. Stability of the solutions was defined as the period for which the one-sided 95% confidence interval of the common regression line remains superior to 90% of the initial concentration as recommended by the U.S. Food and Drug Administration. The forced-degradation tests did not influence the chromatographic peaks of the studied component. No significant change of optic density was seen and no crystals were observed with the optic microscope during the study. The solutions stored at 5°C ± 3°C or at room temperature maintained 90% of their concentration after 24 days. During this period, the pH of the solution decreased from 5.39 to 4.34 at 5°C ± 3°C and from 5.37 to 3.44 at room temperature. In order to alleviate adverse reactions to the eye with too low pH, we propose a period of validity of 15 days at 5°C ± 3°C and 48 hours at room temperature. During this period, the degradation of the preparation was lower than 10%, and the values of pH were higher than 4.0.

Tramadol hydrochloride (Contramal) is often used as infusions for hospitalized patients to manage or prevent acute or chronic pain that requires analgesia at opioid level. Advance preparation of intravenous solutions of tramadol hydrochloride could be useful to improve quality assurance, time management and cost savings of drug delivery; but little is known about their stability after freezing followed by microwave thawing. The purpose of this study was to investigate how freezing, long-term storage and microwave thawing can affect the stability of tramadol in 5% dextrose infusion. The stability of five polyvinyl chloride bags of solution containing 100mg of tramadol/100mL of 5% dextrose was studied after the solution was frozen for 4 months at -20 deg C, followed by thawing in a microwave oven with a validated cycle and final storage at 4 deg C. Concentration of tramadol was measured by high-performance liquid chromatography using a reversed-phase column, a mobile phase consisting of 30% acetonitrile in phosphate bufer pH 2.5 and ultraviolet detecion at 230 nm. Visual inspection and pH measurement were also performed. No color change or precipitation was observed. Tramadol was stable for at least 60 days. Throughout this period, the lower confidence limit of the estimated regression line of the concentration-time profile remained at above 90% of the initial concentration. During this stability period, the pH value decreased slightly without affecting chromatographic parameters. Within these limits, tramadol in 5% dextrose infusion may be prepared frozen in advance by a centralized intravenous admixture service, then thawed before use in clinicl units.

Cefepime is often used in antibiotic infusions for the hospitalized patients. Using intravenous solutions of cefepime prepared in advance can be efficient, but little information is available about the stability of that antibiotic after freezing followed by microwave thawing. The purpose of this study was to investigate how freezing, long-term storage, and microwave thawing can affect the stability of cefepime in 5% dextrose injection. The stability of 5 polyvinyl chloride bags of solution containing 2g of cefepime per 100 mL of 5% dextrose injection was studied after the bags had remained frozen for 1 month at -20 deg C, were thawed in a microwave oven with a validated cycle, and were stored at 4 deg C. The concentration of cefepime was measured by high-performance liquid chromatography by means of a reversed phase column, a mobile phase consisting of 10% acetonitrile and pentane sulfate buffer, and ultraviolet detection at 254 nm with a diode array detecor. Visual inspection was also conducted, and pH measurements were obtained. No color change or precipitation in the solution was observed. Cefepime remained stable for 11 days. During this period, the 95% lower confidence limit of the estimated regression line of the concentration-time profile remained above 90% of the initial concentration and the pH value increased slightly without affecting chromatographic parameters. Within those limits, cefepime may be prepared in advance by a centralized intravenous admixture service; it may be frozen and then thawed in a microwave before use in clinical units.

The advance preparation of intravenous solutions of teicoplanin, which is often used in antibiotic infusions for hospitalized patients, may be advantageous. The objective of this study was to investigate the stability of teicoplanin stored at 4 deg C in polyvinyl chloride bags to determine whether such solutions could be safely stored without deterioration. Five bags containing 0.4g teicoplanin per 100 mL of 5 % dextrose injection were studied for 1 month by means of high-performance liquid chromatography, visual inspection, and pH measurement. The color of teicoplanin diluted in dextrose became slightly yellow, and the pH values of the preparations decreased significantly during the period of the study without affecting the chromatographic parameters. The teicoplanin solution was stable for 6 days at 4 deg C as a result of the shortest shelf life of 90% residual potency of the five major glycopeptide components. Despite the color and pH variations, the teicoplanin infusion remained chemically stable when stored up to 6 days at 4 deg C in polyvinyl chloride bags. Thus the infusion could be prepared in advance by a centralized intravenous admixture service for use within the limits described.