Stability of famotidine 20 and 40 mg/L in total nutrient admixtures

The stability of famotidine in two types of total nutrient admixtures (TNAs), one containing 5% intravenous fat emulsion of long-chain triglycerides and the other, of medium- and long-chain triglycerides, was studied. The TNAs, which contained lipids, glucose, amino acids, electrolytes, vitamins, and trace elements, were prepared aseptically in ethylene-vinyl acetate containers. Famotidine 40 mg was added to both types of TNAs and famotidine 80 mg was added to both types to yield concentrations of 20 and 40 mg/L (expressed hereafter as micrograms per milliliter), respectively. A control solution was prepared for each type of TNA. Samples were removed at 0, 12, 24, 48, and 72 hours for measurement of pH and of famotidine concentration by high-performance liquid chromatography; the solutions were visually inspected for color changes, creaming, and formation of precipitates. Particle size distributions were measured at 72 hours and compared with those for the control solutions at time zero. No appreciable changes in pH occurred over 72 hours, and no physicochemical changes were observed. Famotidine 20 and 40 micrograms/mL was stable for at least 72 hours in both types of TNAs. There was no variation in particle size distribution. Famotidine appears to be stable for up to 72 hours at room temperature in the TNAs studied, and it appears not to alter the integrity of the two lipid emulsions.     

Stability of famotidine 20 and 50 mg/L in total nutrient admixtures

The stability of famotidine in total nutrient admixtures (TNAs) containing dextrose, an intravenous fat emulsion (IVF), and high or low concentrations of amino acids was studied. Famotidine was added to TNA solutions to final concentrations of 20 and 50 mg/L. TNA 1 contained 20% dextrose, IVF 40 g/L, and amino acids 42.5 g/L, and TNA 2 contained 25% dextrose, IVF 25 g/L, and amino acids 21.25 g/L. Control solutions of TNAs 1 and 2 without famotidine were also studied. All solutions were stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. The solutions were observed for signs of creaming or coalescence and measured for pH, famotidine concentration, and particle size at 0, 24, and 48 hours. No signs of creaming or coalescence were observed in control or test solutions throughout the study period. Famotidine in TNAs 1 and 2 showed a less than 5% change in concentration over the 48-hour period. Neither time nor amino acid concentration had any significant effect on famotidine concentration. Similarly, there were no significant differences in emulsion particle size between control solutions and TNAs containing famotidine and no significant changes in particle size over time. Famotidine 20 and 50 mg/L is stable in the TNAs tested when stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. Famotidine did not appear to disrupt the integrity of the emulsion system.     

Stability of ceftazidime and amino acids in parenteral nutrient solutions

The stability of ceftazidime was studied under conditions simulating administration via a Y-injection site into a primary infusion of parenteral nutrient (PN) solution; the stabilities of ceftazidime and amino acids when the drug was added directly to PN solutions were also studied. Three PN solutions containing 25% dextrose were used; the amino acid contents were 0, 2.5%, and 5%. Ceftazidime with sodium carbonate was used to prepare stock solutions of ceftazidime 40 mg/mL in both 0.9% sodium chloride injection and 5% dextrose injection; to simulate Y-site injection, samples were added to the three PN solutions to achieve ceftazidime concentrations of 10 and 20 mg/mL, or 1:1 and 1:3 ratios of drug solution to PN solution. Samples of these admixtures were assayed by high-performance liquid chromatography (HPLC) initially and after room-temperature (22 degrees C) storage for one and two hours. Additional solutions were prepared by adding sterile water for injection to ceftazidime with sodium carbonate; drug solutions were added to each PN solution in polyvinyl chloride bags to achieve ceftazidime concentrations of 1 and 6 mg/mL. The samples were assayed by HPLC for ceftazidime concentration after storage at 22 degrees C for 3, 6, 12, 24, and 36 hours and at 4 degrees C for 1, 3, 7, and 14 days. Amino acid stability was analyzed in admixtures containing 5% amino acids and ceftazidime 6 mg/mL after 24 and 48 hours at 22 degrees C and after 7 and 10 days at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of fluconazole and amino acids in parenteral nutrient solutions.

The stability of fluconazole and amino acids in parenteral nutrient (PN) solutions was studied. Amino acids at three concentrations (1.0%, 2.5%, and 5.0%) with 25% dextrose injection were combined with a high (1.75 mg/mL) or a low (0.5 mg/mL) concentration of fluconazole to form six combinations of PN solution and fluconazole. The solutions were visually inspected for precipitate, color change, or gas formation and tested for pH. By using high-performance liquid chromatography, the solutions were assayed for fluconazole concentration at zero, one, and two hours after preparation. The PN solution containing fluconazole 1.75 mg/mL and 5.0% amino acids was assayed for 14 amino acids at the same time points. There was no visual evidence of incompatibility in any of the fluconazole and PN solutions, and the pH of the solutions did not vary appreciably throughout the study period. The mean percentage of initial fluconazole concentration remaining at one and two hours was greater than 97% for all of the solutions studied. The mean percentage of initial amino acid concentration remaining at one and two hours was greater than 93% for each of the 14 amino acids assayed. When fluconazole 0.5 mg/mL or 1.75 mg/mL is mixed with PN solution containing 1.0%, 2.5%, or 5.0% amino acids and 25% dextrose injection, both fluconazole and amino acids are stable for up to two hours.     

Stability of ranitidine hydrochloride and amino acids in parenteral nutrient solutions

The stability of ranitidine hydrochloride in parenteral nutrient (PN) solutions and the effect of ranitidine hydrochloride on the amino acids in the PN solutions were studied. Six PN solutions (three each with amino acid contents of 2.125 and 4.25%) were prepared. Each PN solution also contained dextrose 25%, electrolytes, trace elements, vitamins, and heparin sodium. Ranitidine hydrochloride injection was added to four of the PN samples. Of the final samples, two contained no ranitidine, two contained ranitidine hydrochloride 50 micrograms/mL, and two contained ranitidine hydrochloride 100 micrograms/mL. Admixtures of ranitidine hydrochloride at the two concentrations in 0.9% sodium chloride injection were also prepared. Samples were observed for color change and tested for pH during storage at room temperature. Concentrations of amino acids were measured after 24 hours in samples without ranitidine and in samples containing ranitidine hydrochloride 100 micrograms/mL. Ranitidine hydrochloride content was determined by high-performance liquid chromatography at 12, 24, and 48 hours. No visual changes or pH changes occurred by 24 hours. All PN solutions became darker by 48 hours. The presence of ranitidine hydrochloride did not substantially affect amino acid concentrations. At 24 hours, at least 90% of the initial ranitidine concentrations remained in all samples. In three of the four PN samples at 48 hours, less than 90% of initial ranitidine concentrations remained. Ranitidine hydrochloride in concentrations of 50 and 100 micrograms/mL in parenteral nutrient solutions containing 4.25 and 2.125% crystalline amino acids is stable for 24 hours at room temperature. Under these conditions, concentrations of the amino acids contained in the PN solutions were not affected by the addition of ranitidine hydrochloride.     

Stability of penicillins in total parenteral nutrient solution

The stability of ticarcillin, mezlocillin, and piperacillin in total parenteral nutrient (TPN) solutions at concentrations commonly used in adults was determined. Each antibiotic was added separately to three different amino acids-dextrose TPN solutions in two concentrations: 10 and 20 mg/mL. Amino acids concentration ranged from 25 g/L to 50 g/L. Dextrose concentration ranged from 100 g/L to 350 g/L. Solutions were assayed for antibiotic concentration immediately after mixing (time 0) and at 4, 8, 24, and 48 hours by high-performance liquid chromatography. The effect of the added penicillins on the stability of amino acids and other TPN additives was not investigated. Mezlocillin and piperacillin 10 and 20 mg/mL exhibited stability in TPN solution at 24 hours. Ticarcillin was stable for 24 hours at a concentration of 10 mg/mL, but at 20 mg/mL it was unstable at all times tested. The three antibiotics demonstrated the same characteristic stability in all three TPN solutions, suggesting that the concentrations of dextrose and amino acids did not affect stability. Ticarcillin, mezlocillin, and piperacillin are stable for 24 hours in the TPN solutions studied.     

Stability of aminophylline injection in three parenteral nutrient solutions

The stability of aminophylline injection in crystalline amino acid-dextrose solutions containing standard additions of electrolytes, vitamins, and minerals was evaluated. Aminophylline injection was added to three parenteral nutrition (PN) solutions in dosages of 0.25-1.50 mg/ml. All of the samples were prepared in duplicate, stored in sealed volumetric flasks, and allowed to stand under normal lighting at room temperature or under refrigeration for 48 hours. Samples were analyzed for theophylline content by reverse phase high-pressure liquid chromatography at 1, 24, and 48 hours. Mean percent theophylline recovery 24 hours after admixture was 101 +/- 10.9%, 101 +/- 4.3%, and 100 +/- 4.3% in the three PN solutions. Solution pH values were stable for 48 hours. Refrigeration and lower amino acid concentrations did not alter stability. Aminophylline is stable in PN solutions for 24 hours in concentrations up to 1.5 mg/ml.     

Stability of ranitidine hydrochloride in total parenteral nutrient solution

The stability of ranitidine hydrochloride was studied in a standard total parenteral nutrition (TPN) solution. The Canadian formulation of ranitidine hydrochloride (25 mg/mL) was added in 100-, 200-, and 300-mg doses to approximately 1200 mL of a TPN solution and allowed to stand at room temperature (23 degrees C) for seven days. During this time, samples were drawn at least once a day, and the ranitidine concentration was determined by high-performance liquid chromatography. The ranitidine concentration declined at roughly the same rate regardless of the initial concentration. During the study period, each of the three different concentrations declined to less than 70% of the initial concentration. Approximately 10% of the initial concentration was lost in 48 hours. Ranitidine hydrochloride admixtures were stable for up to 48 hours at room temperature in this standard TPN solution.     

Amino acid stability and microbial growth in total parenteral nutrient solutions

The stability of amino acids in total parenteral nutrient (TPN) solutions stored for 30 days and the potential for stored TPN solutions to support growth of microbial contaminants were studied. Solutions of 3.5% crystalline amino acids and 25% dextrose with electrolytes were prepared either by using a commercially available amino acid solution with electrolytes or by adding electrolytes individually to a base TPN solution. Solutions were stored in polyvinyl chloride bags at refrigerated (4 degrees C) or room (25 degrees C) temperature for 30 days. Some bags were inoculated with Candida albicans or Pseudomonas maltophilia before storage to serve as positive controls for evaluation of microbial contamination. At appropriate intervals, bags of each type of solution under each storage condition were analyzed for amino acid content. Microbial growth was evaluated by filtering the contents of each bag and incubating the filter in brain-heart infusion broth. No microbial growth was detected in any of the study solutions, but all solutions inoculated with C. albicans and 2 of 16 solutions inoculated with Ps. maltophilia had evidence of growth. No significant decreases in the concentrations of any of the amino acids were noted for solutions stored at refrigerated temperature, but significant decreases in the concentrations of arginine and methionine were noted for solutions stored at room temperature. Total parenteral nutrient solutions can be stored for up to 30 days if they are kept at refrigerated temperatures and protected from light; however, quality assurance measures for these solutions should include end-product microbiologic testing.     

复方氨基酸(19)注射液配制的全静脉营养液稳定性研究及临床应用

目的 考察由新型复方氨基酸(19)丙谷二肽注射液(创伤用)[以下简称复方氨基酸(19)注射液]配制的全静脉营养液的稳定性及应用于人体的安全性.方法 复方氨基酸(19)注射液配制的全静脉营养液在4、25、40℃条件下存放48 h,按中国药典2010年版二部附录要求,观察其外观、不溶性微粒、脂肪乳粒粒径大小和分布、pH值、渗透压的变化,并检查细菌内毒素.通过伦理委员会批准该营养液用于6例健康受试者,考察其应用于人体的安全性、耐受性.结果 观察期内,复方氨基酸(19)注射液配制的全静脉营养液在4、25、40℃条件下不溶性微粒、脂肪乳粒粒径大小和分布、pH值、渗透压均在药典规定的范围内,40℃时外观略有变化.无菌试验和细菌内毒素检查的结果显示,该全静脉营养液无菌、无细菌内毒素.6例健康受试者可安全耐受该全静脉营养液.结论 复方氨基酸(19)注射液配制的全静脉营养液在4、25、40℃条件下存放24 h符合中国药典静脉用注射乳状液的质量要求,应用于人体是安全可耐受的.     

Compatibility considerations in parenteral nutrient solutions

Information on compatibility of nutrients and drugs with parenteral nutrient (PN) solutions is reviewed and evaluated. Precipitation of calcium phosphate when calcium and phosphate salts are added can be affected by pH, amino acid concentration, amino acid product, temperature, sequence of additives, specific salt used, and time since admixture; precipitate formation can occur gradually over 24 hours. Insulin is chemically stable in PN solutions, but adsorption to the infusion system can cause decreased availability. Poor delivery of vitamin A via PN solutions has been reported. The sodium bisulfite content of amino acid injections may cause degradation of thiamine, but studies simulating clinical use are needed. Folic acid stability in PN solutions has been demonstrated, and phytonadione appears to be stable. Drug administration via PN solutions may be advantageous when fluid intake is restricted or peripheral vein access is limited and in home PN therapy. Summarized are results of studies involving heparin, cimetidine hydrochloride, aminophylline, amphotericin B, iron dextran, hydrochloric acid, corticosteroids, narcotics, metoclopramide, digoxin, and fluorouracil. Many antibiotics are probably stable, especially when administered by co-infusion rather than by direct mixture in the PN solution container. When lipids are mixed in the same container with amino acid-dextrose solutions, compatibility and stability of electrolytes, vitamins, and trace elements must be reassessed. Practical research is needed, and availability of additives should be studied in specific patient populations and for specific PN formulations. Valid conclusions are dependent on careful study design.