Chemical Stability of Epinephrine 10 mcg/mL Diluted in 0.9% Sodium Chloride and Stored in Polypropylene Syringes at 4 degrees C and 25 degrees C.

Studies have evaluated epinephrine stability in higher concentrations and shorter durations than we require. The objective of this study was to evaluate the chemical stability of epinephrine in syringes at concentrations of 10 mcg/mL in 0.9% sodium chloride at 4°C and 25°C. Solutions of 10 mcg/mL epinephrine in 0.9% sodium chloride were prepared and stored in 10-mL Becton, Dickinson and Company syringes. Three units of each container were stored at 4°C and 25°C. Concentration analysis was completed on study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91 using a validated stability-indicating liquid chromatographic method with ultraviolet detection. Chemical stability was based on the intersection of the lower limit of the 95% confidence interval of the observed degradation rate and the time to achieve 90% of the initial concentration (T-90). The analytical method separated degradation products from epinephrine to measure concentration specifically, accurately, and reproducibly. During the study period, all solutions at 4°C retained more than 89.62% of the initial concentration for 91 days. Solutions stored at 25°C retained more than 90% for 21 days. Multiple linear regression revealed significant differences in percent remaining due to study day (P<0.001) and temperature (P=0.002). The calculated T-90, with 95% confidence, was 71.40 days for solutions stored at 4°C but only 12.77 days for solutions stored at 25°C. We conclude that 10 mcg/mL epinephrine solution diluted in 0.9% sodium chloride stored at 4°C is chemically and physically stable for 64 days, with 95% confidence. The syringe may be held at room temperature for up to 24 hours during this period and still retain more than 90% of the initial concentration.

Stability of Extemporaneously Compounded Nadolol 10-mg/mL Suspension in Oral Mix in Glass and Plastic Bottles and Plastic Syringes.

An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective of this study was to evaluate the stability of nadolol 10 mg/mL prepared in Oral Mix vehicle and stored in amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride for 91 days at 4ÆC and 25ÆC; and polypropylene oral plastic syringes at 25ÆC only. Three separate batches of nadolol suspension 10 mg/mL were prepared with Oral Mix. Of the suspension, 50-mL aliquots were stored in 100-mL bottles (amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride). Half of the bottles from each container type were stored at 25ÆC and the other half at 4ÆC. On study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91, nadolol concentration was determined using a reverse-phase, stability-indicating liquid chromatographic method from samples drawn from each type of container at each temperature. Oral syringes (3 mL), filled with 2 mL of suspension, were stored at 25ÆC and tested on days 0, 2, 7, 21, 42, and 91. The concentration of nadolol 10 mg/mL in Oral Mix in all study samples from bottles and oral syringes remained within 3.5% of the initial concentration. Based on the fastest degradation rate with 95% confidence, on day 91, between 99% to 100% and 98% to 100% remained in suspensions stored in bottles at 25ÆC and 4ÆC, respectively. Oral syringes at 25ÆC had 94% remaining on day 91. Multiple linear regression analysis demonstrated that the percent remaining was related to study day and container, but not temperature. On day 91, nadolol 10 mg/mL oral suspensions prepared with Oral Mix and stored in all bottle types at 4ÆC will retain more than 98% of the initial concentration compared to 99% at 25ÆC and only 94% when stored in oral syringes.

Stability of Generic Formulations of Bortezomib 1.0 and 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C or 25°C).

BACKGROUND: The availability of generic versions of bortezomib raises questions about the reliability of extrapolating stability data from one brand to another. OBJECTIVE: To evaluate the stability of bortezomib formulations available from Janssen, Teva Canada, Actavis Pharma, Dr. Reddy's Laboratories, Apotex, and MDA, reconstituted with 0.9% sodium chloride (normal saline) to produce solutions of either 1.0 or 2.5 mg/mL and stored over at least 21 days under refrigeration (4°C) or at room temperature (either 23°C or 25°C) in the manufacturer's original glass vials or in polypropylene syringes. METHODS: On study day 0, solutions with concentration 1.0 mg/mL or 2.5 mg/mL of the Teva, Actavis, Dr. Reddy's, Apotex, and MDA generic formulations were prepared. Three units of each type of container (glass vials and syringes) were stored at 4°C and 3 units at room temperature. Concentration and physical inspection were completed on at least 8 study days (including day 0) over a 21- to 84-day study period. Bortezomib concentrations were determined by a validated stability-indicating liquid chromatographic method with ultraviolet detection. The end point of these studies was the time to reach 90% of the initial concentration (T-90) with 95% confidence, which is expressed as "T-9095%CI", where CI refers to the confidence interval. In addition to estimating the T-9095%CI, differences in stability among products from all manufacturers were compared using multiple linear regression. Previously published data for the Janssen product were included in the overall comparisons. RESULTS: In all of the studies, the analytical method separated degradation products from bortezomib, such that the concentration of bortezomib was measured specifically, accurately (deviations < 2.5%), and reproducibly (average replicate error 2.5%). During all studies, solutions retained more than 94% of the initial concentration at 4°C. The T-9095%CI exceeded the study period for all formulations under all combinations of concentration, container, and temperature, except the 84-day study for the MDA product. Multiple linear regression showed no significant differences among manufacturers (p = 0.57). CONCLUSIONS: In this study, formulations of bortezomib currently marketed in Canada (by Janssen, Teva Canada, Actavis Pharma, Dr. Reddy's Laboratories, Apotex, and MDA) were pharmaceutically equivalent and interchangeable. Given that there was no difference in stability related to manufacturer, nominal concentration, or container, we conclude that these formulations are physically and chemically stable for at least 35 days under refrigeration and at least 25 days at room temperature.

CONTEXTE: La disponibilité de versions génériques de bortezomib soulève des questions relatives à la fiabilité de l'extrapolation des données concernant la stabilité d'une marque à l'autre. OBJECTIF: Évaluer la stabilité des formules de bortezomib de Janssen, de Teva Canada, d'Actavis Pharma, des Laboratoires du Dr Reddy, d'Apotex et de MDA, reconstituées avec 0,9 % de chlorure de sodium (solution saline normale) pour produire des solutions de 1 ou de 2,5 mg/mL et réfrigérées au moins 21 jours à 4 °C ou à température ambiante (23 °C ou 25 °C), dans des fioles en verre du fabricant ou dans des seringues en polypropylène. MÉTHODES: La préparation des solutions avec une concentration de 1 mg/mL ou 2,5 mg/mL des formules génériques de Teva, d'Actavis, du Dr Reddy, d'Apotex et de MDA a eu lieu le jour 0 de l'étude. Trois unités de chaque contenant (fioles en verre et seringues) étaient stockées à 4 °C et 3 unités, à température ambiante. L'inspection de la concentration et l'inspection physique ont été réalisées pendant au moins 8 jours (y compris le jour 0) de l'étude qui a duré de 21 à 84 jours. Les concentrations de bortezomib ont été déterminées par une méthode chromatographique liquide validée, indiquant la stabilité à l'aide d'une détection par rayons ultraviolets. Le point final de ces études était le temps nécessaire pour que le produit atteigne 90 % de la concentration initiale (T-90) avec un seuil de confiance de 95 %, exprimé par T-90IC 95 %, IC indiquant l'intervalle de confiance. En plus de l'estimation du T-90IC 95 %, les différences de stabilité des produits de tous les fabricants ont été comparées à l'aide d'une régression linéaire multiple. Les données publiées précédemment sur le produit Jansen sont incluses dans les comparaisons globales. RÉSULTATS: La méthode analytique de toutes les études qui ont été menées a séparé les produits de dégradation du bortezomib de telle manière que la concentration était mesurée de manière spécifique, précise (déviations < 2,5 %) et reproductible (erreur de réplique 2,5 %). Tout au long des études, les solutions ont retenu plus de 94 % de la concentration initiale à 4 °C. Le T-90IC 95 % de toutes les formules dans toutes les combinaisons de concentration, de contenant et de température, dépassait la durée des études, à l'exception du produit MDA dans l'étude de 84 jours. La régression linéaire multiple n'a indiqué aucune différence importante parmi les fabricants (p = 0,57). CONCLUSIONS: Dans cette étude, les formules de bortezomib actuellement commercialisées au Canada (par Janssen, Teva Canada, Actavis Pharma, les Laboratoires du Dr Reddy, Apotex et MDA) étaient équivalentes et interchangeables d'un point de vue pharmaceutique. Puisqu'aucune différence de stabilité, de concentration nominale ou de contenant liée à l'un ou l'autre des fabricants n'a été révélée, nous concluons que ces formules sont physiquement et chimiquement stables pendant au moins 35 jours sous réfrigération et au moins 25 jours à température ambiante.

Stability of extemporaneously compounded temozolomide 10 mg/mL suspensions in Oral Mix SF® in glass and plastic bottles and plastic syringes.

BACKGROUND: Temozolomide oral suspension is not commercially available. OBJECTIVE: To evaluate the stability of three temozolomide 10 mg/mL suspensions prepared in Oral Mix SF® in three container types stored at 4°C and 23°C. METHODS: Using commercial capsules, three separate batches of three different temozolomide 10 mg/mL formulations (Oral Mix SF® with PK-30; PK-30 and citric acid; and neither PK-30 nor citric acid) were made and stored in three container types (amber glass bottles, amber polyethylene terephthalate bottles, and polypropylene oral syringes). The aliquots in each container type were stored protected from light, half at 25°C and half at 4°C. On study days 0, 5, 8, 14, 21, 28, 35, 42, and 56, physical properties of samples from each container type at each temperature were assessed, and the temozolomide concentration was determined using a stability-indicating method. The beyond-use-date (time to achieve 90% of initial concentration calculated using the lower limit of the 95% confidence interval of the observed degradation rate) was calculated. RESULTS: Samples stored at 25°C turned from white to orange within seven days. Temozolomide crystals were observed in all samples. Concentration changes due to study day and temperature (p < 0.001) were observed but not due to container (p = 0.991) or formulation (p = 0.987). The beyond-use-date of all formulations in all container types was 56 days at 4°C and 6 days at 23°C. CONCLUSIONS: We recommend that these temozolomide 10 mg/mL formulations be stored at 4°C and be assigned a beyond-use-date of 30 days.

Development of Stable and Simple Finasteride 333-µg/mL Suspensions that Minimize Occupational Exposure.

Finasteride is not commercially available in a liquid format, which stimulated the development of a stable and simple finasteride suspension formulation. The objectives of this work were to develop and test a finasteride suspension for 1) simplicity to compound, 2) pharmaceutical acceptability, 3) stability, and 4) potential for occupational exposure. The stability of commercial 5-mg finasteride tablets (50 mg/150 mL) was evaluated in water, Oral Mix, and OralMix SF in amber polyethylene terephthalate bottles at 25°C or 4°C. Additional stability studies were carried out using sugar-free Finasteride Powder USP in amber polyethylene terephthalate bottles and tablets in water in polypropylene oral syringes. On study days 0, 1, 3, 7, 14, 28, 38, 49, 63, and 90, the finasteride concentration was determined using a validated stability-indicating liquid chromatographic method. The potential occupational airborne exposure was evaluated by attempting to measure finasteride in 1000 liters of room air following shaking and nebulization. Finasteride suspension/dispersion formulations were prepared in water, Oral Mix, and Oral Mix SF from tablets and pure powder. All formulations retained more than 94.3% of the initial finasteride concentration, with 95% confidence, when stored for up to 90 days at room temperature or 4°C. Simulations of occupational exposure failed to demonstrate the presence of finasteride in room air following attempts to nebulize finasteride mixtures. We conclude that 333-µg/mL suspension/dispersions of finasteride in water or Oral Mix products will have more than 94.3% of the initial finasteride concentration remaining after 90 days, regardless of the formulation, container, or storage temperature. Although we could not detect finasteride in room air, given the analytical limits of the study, we estimate that exposure would unlikely exceed 3.6-µg/1000 liters of room air. Nevertheless, since current regulations are based on "no safe limit," use of primary engineering controls and personal protective equipment as appropriate is recommended.

Administration of Intravenous Ascorbic Acid-Practical Considerations for Clinicians.

Emerging data suggest that intravenous ascorbic acid (AA) may be beneficial in patients with sepsis. Clinicians require data on stability of diluted AA for safe administration. We evaluated the stability of AA diluted in normal saline (NS) or 5% dextrose in water (D5W) solutions over 14 days at 25 °C and at 4 °C, protected from light, using concentrations of 37 mg/mL and 77 mg/mL (Sandoz) and 40 mg/mL and 92 mg/mL (Mylan). We also assessed stability of a 40 mg/mL solution (Mylan) at 25 °C exposed to light for 75 h. Concentrations were measured using liquid chromatographic separation with ultraviolet light detection on days 0, 0.33, 1, 1.33, 2, 3, 4, 7, 10 and 14. By day 14, solutions at 4 °C retained >97.72% of the initial concentration; at 25 °C, solutions retained >88.02% of the initial concentration, but visual changes were evident after day 2. Multiple linear regression demonstrated that study day and temperature (p < 0.001) but not solution type (p = 0.519), concentration (p = 0.677) or manufacturer (p = 0.808) were associated with the percentage remaining. At 75 h, degradation rates were similar in solutions protected from vs. exposed to light. In conclusion, AA solutions are stable for at least 14 days at 4 °C, with protection from light.

Stability of Extemporaneously Compounded Domperidone 5 mg/mL Suspension in Oral Mix in Plastic and Glass Bottles and Plastic Syringes.

BACKGROUND: Domperidone liquid for oral administration is not commercially available in Canada, but is needed for patients who cannot swallow intact tablets. OBJECTIVE: To evaluate the stability of domperidone 5 mg/mL suspensions prepared in Oral Mix vehicle and stored, for up to 91 days, in amber polyvinylchloride (PVC) bottles, amber glass bottles, or amber polyethylene terephthalate (PET) bottles at 4°C or 25°C or in polypropylene oral syringes at 25°C. METHODS: Three separate 300-mL batches of domperidone suspension 5 mg/mL were prepared with Oral Mix vehicle. Fifty-millilitre aliquots of the suspension were stored in 100-mL bottles (amber PVC, amber glass, or amber PET). Half of the bottles of each type were stored at 25°C and half at 4°C. On study days 0, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42, 49, 63, 77, and 91, domperidone concentration was determined, with a validated reverse-phase, stability-indicating liquid chromatographic method, in samples drawn from each type of container stored at each temperature. In addition, 1.5-mL aliquots of a fourth 100-mL batch of suspension were stored in 3-mL oral syringes at 25°C and were tested on the same study days. RESULTS: The concentration of domperidone in all study samples remained above 93% of initial concentration after storage for 91 days. The percent remaining on day 91, based on fastest degradation rate (as represented by the lower limit of the 95% confidence interval [CI]), was at least 92.3% for suspensions stored at 4°C in PVC, glass, and PET bottles. With storage at 25°C, suspensions in PVC and glass bottles retained more than 90% of initial concentration, whereas suspensions in PET bottles and plastic syringes retained 88.9% and 88.0% of initial concentration, respectively. CONCLUSIONS: Because suspensions of domperidone in PET bottles and oral syringes retained less than 90% of their initial concentration on day 91 (based on the 95% CI), it is suggested that such suspensions be stored at 4°C or 25°C in any bottle type or syringe with an assigned beyond-use date not exceeding 75 days.

CONTEXTE: La dompéridone sous forme liquide pour administration orale n'est pas disponible sur le marché au Canada, mais elle est nécessaire pour les patients incapables d'avaler des comprimés entiers. OBJECTIF: Évaluer la stabilité de suspensions de dompéridone de 5 mg/mL préparées dans l'excipient Oral Mix et conservées jusqu'à 91 jours dans des flacons de polychlorure de vinyle (PVC) ambré, de verre ambré ou de polyéthylène téréphtalate (PET) ambré à 4 °C ou à 25 °C ou dans des seringues orales de polypropylène à 25 °C. MÉTHODES: Trois différents lots de 300 mL de suspension de dompéridone de 5 mg/mL ont été préparés à l'aide de l'excipient Oral Mix. Des aliquotes de 50 mL de la suspension ont été entreposées dans des flacons de 100 mL de PVC ambré, de verre ambré ou de PET ambré. La moitié des flacons de chaque type était conservée à 25 °C et l'autre moitié était conservée à 4 °C. Aux jours 0, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42, 49, 63, 77 et 91 de l'étude, les concentrations de dompéridone ont été évaluées sur des échantillons tirés de chaque type de flacons conservés aux deux températures à l'aide d'une épreuve validée mesurant la stabilité par chromatographie liquide en phase inverse. De plus, des aliquotes de 1,5 mL provenant d'un quatrième lot de suspension ont été entreposées dans des seringues orales de 3 mL à 25 °C et ont été analysées aux mêmes jours. RÉSULTATS: Les concentrations de dompéridone dans l'ensemble des échantillons de l'étude conservaient plus de 93 % de la concentration initiale après un entreposage de 91 jours. Le pourcentage restant au jour 91, selon le taux de dégradation le plus rapide (correspondant à la limite inférieure de l'intervalle de confiance (IC) de 95 %), atteignait au moins 92,3 % pour les suspensions entreposées à 4 °C dans les flacons de PVC, de verre et de PET. Lorsqu'elles étaient entreposées à 25 °C, les suspensions contenues dans les flacons de PVC ou de verre conservaient plus de 90 % de la concentration initiale alors que les suspensions contenues dans les flacons de PET ou les seringues de plastique conservaient respectivement 88,9 % et 88,0 % de la concentration initiale. CONCLUSIONS: Comme les suspensions entreposées dans les flacons de PET et les seringues orales conservaient moins de 90 % de leur concentration initiale au jour 91 (selon l'IC de 95 %), on suggère d'entreposer les suspensions de dompéridone à 4 °C ou à 25 °C dans n'importe lequel contenant en l'accompagnant d'une date limite d'utilisation ne dépassant pas 75 jours.

Extended Stability of Sodium Phosphate Solutions in Polyvinyl Chloride Bags.

BACKGROUND: Sodium phosphate injection is used to treat moderate to severe hypophosphatemia. There have been no published reports documenting the physical compatibility or chemical stability of sodium phosphate injection in IV solutions. OBJECTIVE: To evaluate the physical compatibility and chemical stability of 30 and 150 mmol/L solutions of phosphate, prepared from sodium phosphate injection, in 5% dextrose in water (D5W) and in 0.9% sodium chloride (normal saline [NS]) and stored in polyvinyl chloride (PVC) bags at 23°C or 4°C over 63 days. METHODS: On study day 0, solutions of phosphate 30 and 150 mmol/L in D5W or NS were prepared in PVC bags and stored at 4°C and 23°C. On prespecified days during the 63-day study period, the concentrations of sodium and phosphate were determined, and admixture weight was checked to assess moisture loss during storage without a plastic overwrap. Chemical stability was calculated from the intersection of the lower 95% confidence limit of the degradation rate and the lower limit of acceptability (90%) for concentration remaining. RESULTS: The analytical methods for both sodium and phosphate were found to be precise (coefficient of variation averaging less than 1% for pre-study validation samples). Both sodium and phosphate retained more than 94% of the initial concentration over the 63-day study period. With 95% confidence, the time to achieve 90% of the initial concentration of both sodium and phosphate approached or exceeded the 63-day study period, regardless of temperature, concentration, or base solution. CONCLUSIONS: Sodium phosphate solutions at a phosphate concentration of 30 or 150 mmol/L in either NS or D5W retained more than 94% of the initial concentration of both sodium and phosphate over 63 days when stored at 23°C or 4°C. In compliance with United States Pharmacopeia General Chapter <797> recommendations, a beyond-use date of 14 days (with refrigeration) or 48 h (room temperature) may be applied. Extending the beyond-use date beyond these limits may be considered, if a validated sterility test is performed.

CONTEXTE: Le phosphate de sodium injectable est employé pour traiter l'hypophosphatémie modérée et grave. À ce jour, aucun rapport portant sur la compatibilité physique ou la stabilité chimique du phosphate de sodium injectable contenu dans les solutions intraveineuses n'a été publié. OBJECTIF: Évaluer la compatibilité physique et la stabilité chimique de solutions de phosphate à des concentrations de 30 et de 150 mmol/L préparées à partir de phosphate de sodium injectable dilué dans du dextrose à 5 % dans l'eau (D5E) ou du chlorure de sodium à 0,9 % (solution physiologique salée [SP]) puis rangées dans des sacs de polychlorure de vinyle (PVC) à des températures de 4 °C ou de 23 °C pendant 63 jours. MÉTHODES: Au jour 0 de l'étude, les solutions de phosphate à des concentrations de 30 et de 150 mmol/L ont été préparées avec du D5E ou de la SP dans des sacs de PVC, puis entreposées à des températures de 4 °C ou de 23 °C. À des jours donnés pendant la période de 63 jours de l'étude, on a évalué les concentrations de sodium et de phosphate et l'on a pesé les mélanges pour vérifier la perte d'humidité pendant un entre-posage n'utilisant pas de suremballage de plastique. La stabilité chimique était calculée au point d'intersection entre la limite inférieure de confiance à 95 % du taux de dégradation et la limite inférieure d'acceptabilité (90 %) de la concentration restante. RÉSULTATS: Les méthodes analytiques employées pour évaluer le sodium et le phosphate se sont révélées précises (coefficient de variation moyen inférieur à 1 % pour les échantillons aux fins de validation avant l'étude). Le sodium et le phosphate conservaient chacun plus de 94 % de leurs concentrations initiales pendant la période d'étude de 63 jours. Avec un niveau de confiance de 95 %, le temps nécessaire pour atteindre 90 % de la concentration initiale pour le sodium et pour le phosphate approchait ou dépassait les 63 jours de la période d'étude, peu importe la température, la concentration ou la solution de base. CONCLUSIONS: Les solutions de phosphate de sodium dont la concentration en phosphate est de 30 ou de 150 mmol/L, qu'elles soient à base de D5E ou de SP, conservaient plus de 94 % des concentrations initiales de sodium et de phosphate pendant 63 jours, qu'elles soient entreposées à des températures de 4 °C ou de 23 °C. Conformément aux recommandations contenues dans le chapitre <797> de la United States Pharmacopeia, une date limite d'utilisation de 14 jours (sous réfrigération) ou de 48 heures (à température ambiante) peut être utilisée. Allonger la date limite d'utilisation au-delà des bornes fixées par l'organisme américain peut être envisageable si une épreuve validée de stérilité est réalisée.

Stability of Ertapenem 100 mg/mL in Manufacturer's Glass Vials or Syringes at 4°C and 23°C.

BACKGROUND: Prophylactic administration of ertapenem as a single 1-g IV dose has been shown to reduce sepsis after prostate biopsy. OBJECTIVE: To evaluate the stability of ertapenem after reconstitution with 0.9% sodium chloride to a final concentration of 100 mg/mL and storage in the manufacturer's original glass vials or polypropylene syringes. METHODS: On study day 0, 100 mg/mL solutions of ertapenem were retained in the manufacturer's glass vials or packaged in polypropylene syringes and stored at 4°C or 23°C without protection from fluorescent room light. Samples were assayed periodically over 18 days using a validated, stability-indicating liquid chromatographic method with ultra-violet detection. A beyond-use date was determined as the time for the concentration to decline to 90% of the initial (day 0) concentration, based on the fastest degradation rate, with 95% confidence. RESULTS: Reconstituted solutions stored in the manufacturer's glass vials or polypropylene syringes exhibited a first-order degradation rate, such that 10% of the initial concentration was lost in the first 2.5 days when stored at 4°C or within the first 6.75 h when stored at room temperature (23°C). Analysis of variance showed differences in the percentage remaining due to temperature (p < 0.001) and study day (p < 0.001) but not type of container (p = 0.98). When a 95% CI for the degradation rate was calculated and used to determine a beyond-use date, it was established that more than 90% of the initial concentration would remain for 2.35 days at 4°C and for 0.23 day (about 5 h, 30 min) at room temperature. CONCLUSIONS: A 100 mg/mL ertapenem solution stored in the manufacturer's glass vial or a polypropylene syringe will retain more than 90.5% of the initial concentration when stored for 48 h at 4°C and for an additional 1 h at 23°C.

CONTEXTE: Il a été démontré que l'administration prophylactique d'une dose unique de 1 g d'ertapénem par voie intraveineuse réduit les risques de sepsis après une biopsie de la prostate. OBJECTIF: Évaluer la stabilité de l'ertapénem reconstitué avec une solution de chlorure de sodium à 0,9 % pour atteindre une concentration finale de 100 mg/mL et placé dans les fioles de verre d'origine du fabricant ou dans des seringues de polypropylène. MÉTHODES: Au jour 0 de l'étude, des solutions de 100 mg/mL d'ertapénem ont été conservées dans les fioles de verre d'origine du fabricant ou conditionnées dans des seringues de polypropylène. Elles ont ensuite été entreposées à des températures de 4 °C ou de 23 °C sans protection contre la lumière des lampes fluorescentes de la pièce. Les échantillons ont été dosés périodiquement pendant 18 jours à l'aide d'une épreuve validée mesurant la stabilité par chromatographie liquide avec détection ultraviolette. Une date limite d'utilisation a été établie comme étant le temps nécessaire pour atteindre 90 % de la concentration initiale (jour 0), et ce, en fonction du taux de dégradation le plus rapide, avec un niveau de confiance de 95 %. RÉSULTATS: Les solutions reconstituées placées dans les fioles de verre du fabricant ou dans les seringues de polypropylène ont présenté un taux de dégradation de premier ordre, de sorte que la concentration initiale avait chuté de 10 % après les 2,5 premiers jours d'entreposage à 4 °C ou après les 6,75 premières heures d'entreposage à température ambiante (23 °C). L'analyse de variance a montré des différences dans le pourcentage restant qui étaient associées à la température (p < 0,001) et au jour de l'étude (p < 0,001), mais pas au type de contenant (p = 0,98). Lorsqu'un intervalle de confiance de 95 % pour le taux de dégradation a été calculé et utilisé pour déterminer la date limite d'utilisation, on a établi qu'il resterait plus de 90 % de la concentration initiale pendant 2,35 jours à 4 °C et pendant 0,23 jour (environ 5 heures 30 minutes) à température ambiante. CONCLUSIONS: Une solution de 100 mg/mL d'ertapénem placée dans la fiole de verre du fabricant ou dans une seringue de polypropylène conserve plus de 90,5 % de sa concentration initiale après avoir été entreposée pendant 48 heures à 4 °C et pendant 1 heure additionnelle lorsqu'elle est entreposée à 23 °C.

Stability of Bortezomib 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C).

BACKGROUND: Solutions of bortezomib 1.0 mg/mL for IV administration are reportedly stable for up to 42 days. Recent publications have reported that the safety profile of bortezomib is better with subcutaneous administration than with IV administration. OBJECTIVE: To evaluate the stability of higher-concentration bortezomib solutions for subcutaneous administration (i.e., 2.5 mg/mL in 0.9% sodium chloride [normal saline or NS]). METHODS: On study day 0, twelve 3.5-mg vials of powdered bortezomib were each reconstituted with 1.4 mL of NS to prepare solutions with concentration 2.5 mg/mL. Half of the solutions were subsequently stored in the original vials and half were transferred to syringes. Three of each type of container were stored in the refrigerator (4°C) and the other 3 of each type were stored at room temperature (23°C). Concentration analysis and physical inspection were completed on study days 0, 1, 2, 8, 12, 14, 19, and 21. The concentration of bortezomib was determined by a validated liquid chromatographic method with ultraviolet detection. The expiry date was determined according to the time to achieve 90% of the initial concentration, based on the fastest degradation rate calculated from the 95% confidence interval of the observed degradation rate. RESULTS: The analytical method separated degradation products from bortezomib such that the concentration was measured specifically and accurately (with absolute deviations from known concentration averaging 2.99%), with intraday and interday reproducibility averaging 1.51% and 2.51%, respectively. During the study period, all solutions were observed to retain at least 95.26% of the initial concentration in both types of containers at both temperatures. CONCLUSIONS: Bortezomib (3.5 mg in manufacturer's vial) reconstituted with 1.4 mL NS is physically and chemically stable for up to 21 days at 4°C or 23°C when stored in either the manufacturer's original glass vial or a syringe. Subcutaneous injection of bortezomib represents a change in practice, and there is a potential safety concern if a solution of the increased concentration used for subcutaneous administration (2.5 mg/mL) is inadvertently used to prepare a dose intended for IV administration. Therefore, it is recommended that sites switching to subcutaneous administration of bortezomib eliminate 1.0 mg/mL IV solutions altogether or institute substantial barriers to prevent IV administration of the higher concentration of bortezomib.

CONTEXTE: Les solutions de bortézomib de 1,0 mg/mL pour administration intraveineuse sont jugées stables pour une période allant jusqu'à 42 jours. Des publications récentes indiquent que le profil d'innocuité du bortézomib est meilleur par administration sous-cutanée que par administration intraveineuse. OBJECTIF: Évaluer la stabilité de solutions de bortézomib à concentration plus élevée pour l'administration sous-cutanée (c.-à-d., 2,5 mg/mL dans du chlorure de sodium à 0,9 % [solution physiologique salée ou SP]). MÉTHODES: Au jour 0 de l'étude, on a reconstitué douze fioles de 3,5 mg de bortézomib sous forme de poudre avec 1,4 mL de SP par fiole afin d'obtenir des solutions d'une concentration de 2,5 mg/mL. La moitié de ces solutions a ensuite été entreposée dans les fioles d'origine et l'autre moitié a été placée dans des seringues. Trois seringues et trois fioles ont été entreposées au réfrigérateur (4 °C) alors que trois fioles et trois seringues ont été entreposées à la température ambiante (23 °C). Une analyse de la concentration ainsi qu'une inspection physique ont été effectuées aux jours 0, 1, 2, 8, 12, 14, 19 et 21 de l'étude. La concentration de bortézomib a été déterminée à l'aide d'une épreuve validée par chromatographie liquide avec détection ultraviolette. La durée de conservation a été établie en fonction du temps nécessaire pour atteindre 90 % de la concentration initiale, selon le taux de dégradation le plus rapide calculé grâce à l'intervalle de confiance à 95 % du taux de dégradation observé. RÉSULTATS: La méthode analytique a séparé le bortézomib de ses produits de dégradation de manière que la concentration a été mesurée de façon spécifique et précise (l'écart absolu par rapport à la concentration connue était en moyenne de 2,99 %), avec une reproductibilité moyenne intrajournalière et interjournalière respectivement de 1.51 % et de 2.51 %. Pendant l'étude, toutes les solutions conservaient au moins 95,26 % de la concentration initiale aux deux températures dans les fioles et les seringues. CONCLUSIONS: La solution obtenue à partir de la reconstitution du contenu d'une fiole de 3,5 mg de bortézomib (fiole du fabricant) avec 1,4 mL de SP est physiquement et chimiquement stable pendant une période allant jusqu'à 21 jours à des températures de 4 °C ou 23 °C lorsqu'elle est entreposée dans la fiole de verre d'origine du fabricant ou dans une seringue. L'injection sous-cutanée de bortézomib représente un changement dans la pratique. Une inquiétude demeure à propos d'un risque possible pour la sécurité des patients si une solution à concentration plus élevée (2,5 mg/mL), destinée à l'administration sous-cutanée, est utilisée par mégarde pour la préparation d'une dose à administrer par voie intraveineuse. Il est donc recommandé que les établissements qui se tournent vers l'administration sous-cutanée de bortézomib éliminent toutes les solutions de 1,0 mg/mL destinées à l'administration intraveineuse ou qu'ils mettent en place des obstacles importants pour éviter l'administration intraveineuse de solutions de bortézomib à concentration élevée. [Traduction par l'éditeur].

Stability of azacitidine in sterile water for injection.

BACKGROUND: The product monograph for azacitidine states that once reconstituted, the drug may be held for only 30 min at room temperature or 8 h at 4°C. Standard doses result in wastage of a portion of each vial, and the cost of this wastage is significant, adding about $156 000 to annual drug expenditures at the authors' institution. OBJECTIVE: To evaluate the stability of azacitidine after reconstitution. METHODS: Vials of azacitidine were reconstituted with sterile water for injection. At the time of reconstitution, the temperature of the diluent was 4°C for samples to be stored at 4°C or -20°C and room temperature for samples to be stored at 23°C. Solutions of azacitidine (10 or 25 mg/mL) were stored in polypropylene syringes and glass vials at room temperature (23°C), 4°C, or -20°C. The concentration of azacitidine was determined by a validated, stability-indicating liquid chromatographic method in serial samples over 9.6 h at room temperature, over 4 days at 4°C, and over 23 days at -20°C. The recommended expiry date was determined on the basis of time to reach 90% of the initial concentration according to the fastest observed degradation rates (i.e., lower limit of 95% confidence interval). RESULTS: Azacitidine degradation was very sensitive to temperature but not storage container (glass vial or polypropylene syringe). Reconstitution with cold sterile water reduced degradation. At 23°C, 15% of the initial concentration was lost after 9.6 h; at 4°C, 32% was lost after 4 days; and at -20°C, less than 5% was lost after 23 days. CONCLUSIONS: More than 90% of the initial azacitidine concentration will be retained, with 97.5% confidence, if, during the life of the product, storage at 23°C does not exceed 2 h, storage at 4°C does not exceed 8 h, and storage at -20°C does not exceed 4 days. These expiry dates could substantially reduce wastage and cost where the time between doses does not exceed 4 days.

Stability of Ibuprofen solutions in normal saline or 5% dextrose in water.

BACKGROUND: A shortage of the standard medication for treatment of patent ductus arteriosus has necessitated use of parenteral ibuprofen, which is equally efficacious for this indication. The beyond-use date recommended by the manufacturer is very short and has implications for resource allocation and wastage. OBJECTIVE: To evaluate the stability of ibuprofen (undiluted or diluted in either 0.9% sodium chloride [normal saline; NS] or 5% dextrose in water [D5W]) with storage for up to 21 days under refrigeration or at room temperature in glass vials or polypropylene syringes. METHODS: Six glass vials, each containing undiluted ibuprofen (5 mg/mL), were prepared. In addition, ibuprofen was diluted to 2.5 mg/mL in NS or D5W, and 6 syringes were prepared for each diluent (total of 12 syringes). Finally, 6 extension tubes were each primed with 1 mL of ibuprofen (duplicates of undiluted solution and solutions diluted to 2.5 mg/mL in NS or D5W). Half of the vials, syringes, and tubes were stored under refrigeration (4°C) and the other half at room temperature (23°C). The concentration of ibuprofen was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 3, 6, 8, 10, 13, 17, and 21 for samples stored in vials and syringes, or at time 0, 6, 24, and 30 h for samples stored in tubes. RESULTS: Analysis of variance showed differences in the percentage of ibuprofen remaining due to study day (p < 0.001) and diluent (p < 0.005), but no differences due to concentration (p = 0.06) or temperature (p = 0.12). All solutions of ibuprofen were stable throughout the study period, retaining at least 90% of their initial concentration. CONCLUSIONS: Undiluted ibuprofen (5 mg/mL) stored in glass vials and ibuprofen diluted to 2.5 mg/mL with either NS or D5W and stored in polypropylene syringes will retain more than 92% of its initial concentration with storage for up to 14 days at 4°C. A beyond-use date of 14 days would allow for up to 24 h storage at 23°C during this 14-day period. Storage of ibuprofen solutions in extension tubing should not exceed 29 h at 4°C or 17 h at 23°C. Beyond-use dates should be applied only after consideration of US Pharmacopeia Revised General Chapter <797> guidelines for compounding of sterile preparations.

Stability of norepinephrine solutions in normal saline and 5% dextrose in water.

BACKGROUND: Most previous stability studies for norepinephrine have reported the percentage of drug remaining in IV solutions after only 24 h. No previously published study has evaluated the effect of light on the stability of this drug. OBJECTIVE: To evaluate the stability of norepinephrine (64 mg/L) in either normal saline (NS; 0.9% sodium chloride) or 5% dextrose in water (D5W) with storage at either 4°C or room temperature (23°C) in polyvinyl chloride (PVC) bags exposed to or protected from normal room lighting for 2 months. METHODS: Thirty-two PVC bags were prepared, each containing norepinephrine at 64 mg/L; half of the bags had normal saline as the diluent and the other half had D5W. The bags were stored at either 4°C or room temperature (23°C), with protection from or exposure to ambient fluorescent room light. Overall, there were 4 bags for each combination of diluent, temperature, and light condition. The concentration of norepinephrine in each bag was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 3, 4, 8, 9, 10, 11, 14, 18, 21, 23, 25, 28, 30, 36, 42, and 61. RESULTS: Analysis of variance revealed differences in percentage remaining as a function of study day (p < 0.001) and light conditions (p < 0.001), but not diluent (p = 0.06) or storage temperature (p > 0.99). CONCLUSIONS: Solutions of norepinephrine 64 mg/L in NS or D5W can be stored in PVC bags at 4°C for up to 61 days with protection from light. This expiry date allows for up to 24 h storage at 23°C. Solutions that are not protected from light will retain only 90% of the initial concentration after storage for 39 days at 4°C. This storage period could include up to 24 h at room temperature, without protection from light.

Stability of commonly used antibiotic solutions in an elastomeric infusion device.

BACKGROUND: The Accufuser silicone-based elastomeric infusion device has recently been approved for the Canadian market. OBJECTIVE: To evaluate the stability of 5 antibiotics (cefazolin, ceftazidime, ceftriaxone, clindamycin, and vancomycin) in either 5% dextrose in water (D5W) or 0.9% sodium chloride in water (NS) after storage in Accufuser disposable silicone balloon infusers. METHODS: The study drugs were reconstituted, according to the manufacturers' directions, in polyvinyl chloride minibags with either D5W or NS, at 2 different concentrations. The resulting solutions were transferred to disposable silicone balloon infusers for storage at 4°C or at room temperature (23°C). The concentration of each drug in each solution was determined by validated stability-indicating liquid chromatographic methods after storage for 14 to 31 days. RESULTS: Solutions of ceftriaxone in either diluent retained more than 95.2% of the initial concentration for 2 days at room temperature and more than 91.6% of the initial concentration for 14 days at 4°C. Solutions of cefazolin in D5W or NS retained more than 90% of the initial concentration for at least 3 days at room temperature and for at least 26 days at 4°C. Solutions of ceftazidime in D5W or NS retained more than 90% of the initial concentration for only 1 day when stored at room temperature and for at least 4 days at 4°C. Solutions of clindamycin or vancomycin in D5W or NS retained 90% of the initial concentration for at least 7.5 days at room temperature and at least 90% of the initial concentration for at least 27.8 days at 4°C. CONCLUSIONS: Previously reported expiration dates for solutions stored in elastomeric infusion devices were not based on 95% confidence intervals and were often longer than expiration dates determined from the studies reported here, which are based on 95% confidence intervals. Comparison of the observed concentrations remaining between previously published studies and the studies reported here indicates that the Accufuser elastomeric infusion device did not adversely affect the stability of these drugs.

Antibiotic lock: in vitro stability of vancomycin and four percent sodium citrate stored in dialysis catheters at 37 degrees C.

Catheter-related bacteremia (CRB) is a major cause of morbidity and mortality especially among patients receiving hemodialysis (HD). Antibiotic lock therapy represents a promising technique in the treatment of CRB. Several studies have evaluated antibiotics in combination with heparin as an interdialytic locking solution as adjunctive therapy for CRB. The objective of this study was to evaluate the chemical stability of the vancomycin in 4% sodium citrate in HD catheters as an interdialytic lock. Vancomycin was prepared and diluted with sodium citrate 4% and stored in polyvinyl chloride syringes, 2 carbothane dialysis catheters (Hemostar) and 2 dual floating HD catheters (CardioMed). Syringes were stored at 4 degrees C or 23 degrees C and the catheters were stored in an incubator at 37 degrees C for 72 hours. Samples underwent daily chromatographic analysis and the luminal concentration of vancomycn was determined on study days 0, 1, and 3. When vancomycin is reconstituted with normal saline to achieve a concentration of 50 mg/mL, and then further diluted in 4% sodium citrate, to achieve concentrations of either 1 or 3 mg/mL, and then stored at 4 degrees C, room temperature, or 37 degrees C, solutions were observed to retain >92% of the initial concentration for the study period of 3 days. Based on the fastest degradation rate determined with 95% confidence interval, >90% is retained for 6.53 days. We conclude that vancomycin-4% citrate solutions stored in polyvinyl chloride syringes or HD catheters are not significantly affected by temperature or concentration within the 72 hours storage period. Therefore, these solutions can be anticipated to be suitable as a HD interdialytic antibiotic lock in standard HD catheters.

Bridging the gap: an innovative dementia learning program for healthcare assistants in hospital wards using facilitator-led discussions.

Nursing a person with dementia in a ward setting can be stressful and a challenge for staff and patients alike. Healthcare assistants are identified as requiring a specific training program. They form part of the front-line workforce and yet have the least access to training but often most contact with patients. The program in this study focused on person-centered care and used six self-study workbooks. Experienced registered nurses are trained to be facilitators of 12 group discussions in the ward setting. The training program viewed the facilitator as playing a key role in empowering the healthcare assistant but also in promoting reflective practice. The outcomes to date have been positive and showed a development in confidence and competence of the healthcare assistants involved.

Make education a priority.

I welcomed the coverage of the National Dementia Strategy for England (Nursing Older People, February 2009).

Extended stability of pantoprazole for injection in 0.9% sodium chloride or 5% dextrose at 4°c and 23°c.

BACKGROUND: The pantoprazole product available in Canada for IV administration has recently been reformulated to include ethylenediaminetetra-acetic acid (EDTA). The purpose of this study was to determine if the chemical stability of pantoprazole for injection containing EDTA (PANTO IV), admixed in polyvinyl chloride (PVC) minibags at concentrations of 0.16 mg/mL and 0.80 mg/mL in 5% dextrose in water (D5W) or 0.9% sodium chloride for injection (normal saline [NS]) and stored at 4°C or 23°C, could be extended beyond the manufacturer's expiry period of 24 hours. METHODS: Sodium pantoprazole was reconstituted in NS or D5W, and 32 PVC minibags were prepared, 16 containing pantoprazole at a nominal concentration of 0.16 mg/mL (8 in NS, 8 in D5W) and 16 containing pantoprazole at a nominal concentration of 0.80 mg/mL (8 in NS, 8 in D5W). Half of the minibags for each diluent-concentration combination were stored at 4°C and half at room temperature (23°C). The concentration of pantoprazole in each minibag was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 4, 7, 9, 11, 14, and 21. RESULTS: Analysis of variance revealed differences in the percentage of drug remaining in relation to temperature (p < 0.001), study day (p = 0.001), concentration (p = 0.007), and diluent (p = 0.008). CONCLUSIONS: Solutions of pantoprazole in D5W with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for a maximum of 11 days at 4°C plus an additional 6 h at 23°C. The saline solutions degraded more slowly, and pantoprazole admixtures in NS with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for 20 days at 4°C plus an additional 6 h at 23°C. Under these conditions, more than 90% of the initial concentration will remain (with 95% confidence).