Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Aminosyn PF

Factors affecting the solubility of calcium and phosphate in neonatal total parenteral nutrient (TPN) solutions containing a new amino acid formulation were studied. Six TPN solutions containing various concentrations of Aminosyn PF, an amino acid solution for infants and children, were prepared in 10% dextrose injection. Some of the solutions also contained cysteine hydrochloride 40 mg per gram of protein. Various concentrations of calcium gluconate and monobasic and dibasic potassium phosphate were added to 20-mL samples of the TPN solutions. A total of 27 samples of each TPN solution was prepared. Samples were visually inspected after 18 hours at 25 degrees C and again after 30 minutes in a water bath at 37 degrees C. Clear samples at this time were also examined microscopically. Solubility curves were prepared by plotting the concentrations at which either visual or microscopic precipitation occurred. Solubility curves for TPN formulations containing Aminosyn PF revealed a decrease in calcium solubility of 5 to 15 meq/L and a decrease in phosphate solubility of 5 to 15 mmol/L compared with previously published calcium-phosphate solubility curves for another similar amino acid solution, TrophAmine. Calcium and phosphate solubilities were also influenced by temperature and the time after solution preparation. In these TPN formulations containing Aminosyn PF as the amino acid source, the solubilities of calcium and phosphate were substantially less than reported in a previous study of solutions containing TrophAmine.     

Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing TrophAmine

Factors affecting solubilities of calcium and phosphate in neonatal total parenteral nutrient (TPN) solutions containing a new amino acid formulation were examined. Twelve TPN solutions containing various concentrations of TrophAmine, an amino acid formulation specific for infants and young children, were prepared in 10% dextrose injection. Some of the solutions also contained cysteine hydrochloride 40 mg/g of protein and either sodium bicarbonate or hydrochloric acid (lipid emulsion buffer) to buffer the solution pH to simulate that produced by simultaneously administering lipid emulsion through the i.v. line. Calcium gluconate and monobasic and dibasic potassium phosphate were added to 20-mL samples of the TPN solutions to achieve calcium concentrations of 10, 20, 30, 40, or 50 meq/L with phosphate concentrations of either 10, 20, 30, or 40 mmol/L; a total of 20 samples of each TPN solution was prepared. Samples were inspected visually for precipitation or crystallization after 18 hours at 25 degrees C and again after 30 minutes in a water bath at 37 degrees C. Clear samples at this time were also examined microscopically for evidence of microcrystallization. Solubility curves were prepared by plotting graphically the concentrations at which either visual or microscopic precipitation occurred. Temperature, amino acid concentration, and the addition of cysteine hydrochloride and lipid emulsion buffer each influenced the solubilities of calcium and phosphate in the TPN solutions. The use of TrophAmine as the amino acid source allowed slightly greater concentrations of phosphate to be solubilized as compared with older amino acid formulations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Aminosyn-PF or TrophAmine

The maximum solubilities of calcium and phosphate in neonatal total parenteral nutrient (TPN) solutions compounded using Aminosyn-PF or TrophAmine amino acid injection were determined. Eight solutions were compounded from Sterile Water for Injection, USP, 50% dextrose injection, usual electrolytes and trace metals, and Aminosyn-PF 7% or TrophAmine 6% to obtain concentrations of amino acids 2.5% and dextrose 25% and amino acids 1% and dextrose 10%. Cysteine hydrochloride was added to half of the solutions at a concentration of 40 mg/g of protein. The pH of each solution was determined at various times during admixture preparation. The solutions were divided into 20-mL aliquots, and phosphate and calcium were added to each aliquot at concentrations of 2.5 to 50 meq/L of calcium and 5 to 50 mmol/L of phosphate. All solutions were inspected visually for signs of precipitation or crystallization after 18 hours of storage at room temperature and again after 30 minutes in a 37 +/- 1 degrees C water bath. Samples with no visible signs of precipitation were filtered, and the filter membrane was inspected under a microscope. Solubility curves were prepared by plotting the concentrations of calcium and phosphate at which either visual or microscopic precipitation occurred. Calcium and phosphate solubility was greater in the solutions with higher concentrations of amino acids and dextrose. In contrast to the results of some previous studies, no important differences in calcium and phosphate solubility were observed between Aminosyn-PF and TrophAmine in solutions containing amino acid concentrations of 2.5%, with or without added cysteine hydrochloride.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of amiodarone hydrochloride in admixtures with other injectable drugs

The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.     

Compatibility and stability of electrolytes, vitamins and antibiotics in combination with 8% amino acids solution

The compatibility and stability of the following additives in an 8% amino acids and 50% dextrose solution intended for total parenteral nutrition were studied: potassium phosphate, calcium gluconate, magnesium sulfate, multiple vitamine mixtures, folic acid, cyanocobalamin, phytonadione, insulin, ampicillin, cephalothin, kanamycin and gentamicin. In addition to physical examination, techniques of ultraviolet spectroscopy, thin-layer chromatography and microbiologic assay were used to delineate compatibility characteristics. The principle compatibility problems are generated by elevated concentrations of calcium and phosphate. The efficacy of ampicillin, cephalothin and kanamycin in the amino acids/dextrose solution, with or without additives, did not appear to be significantly different from control samples prepared in sterile water. It appeared that gentamicin might be significantly more effective in the test solutions than in sterile water, but further investigation is needed to verify this. A comprehensive study of the stability of vitamins in parenteral nutrient solutions must be made before a final judgment can be made.     

葡萄糖酸钙注射液与注射用地塞米松磷酸钠的输液配伍相容性

目的：考察葡萄糖酸钙注射液和注射用地塞米松磷酸钠在输液袋中的配伍相容性。方法：模拟临床输液实际情况,在室温（25℃）下,将临床常用量葡萄糖酸钙在10%葡萄糖注射液或0.9%氯化钠注射液输液袋中与注射用地塞米松磷酸钠混合配伍,分别在0,0.5,1,3 h考察外观、pH及葡萄糖酸钙和地塞米松磷酸钠的药物浓度。结果：上述配伍输液在3 h内均无浑浊、变色、沉淀和气体产生等,pH保持稳定,而地塞米松磷酸钠的浓度随时间在输液中呈现不同程度的变化。结论：临床常用量葡萄糖酸钙注射液与注射用地塞米松磷酸钠在常用输液中存在配伍禁忌。     

Compatibility of common additives in protein hydrolysate/dextrose solutions.

The compatibility of common additives in protein hydrolysate/dextrose solutions was studied. The additives included electrolytes (calcium gluconate, potassium phosphate and magnesium sulfate), vitamins (M.V.I., Solu B Forte, phytonadione, cyanocobalamin and folic acid), insulin and heparin sodium. Various concentrations of the admixtures were observed at intervals throughout a 24-hour period. Combinations which displayed no physical change were subjected to spectrophotometric analysis. Thin-layer chromatography was used to examine those mixtures which displayed a spectral change. The principal incompatibility problems are related to concentrations of calcium gluconate and potassium phosphate. The order of mixing affected the concentration tolerances. The vitamins, insulin, heparin and magnesium, in usual therapeutic concentrations, appeared to be compatible in the protein hydrolysate/dextrose solution.     

Growth of bacteria and fungi in parenteral nutrition solutions containing albumin

The ability of total parenteral nutrition (TPN) solutions containing albumin to support bacterial and fungal growth was studied. The following solutions were tested for microbial growth: (A) thioglycolate broth, (B) solution A with preservatives, (C) albumin 6.25 g in 500 ml 0.9% sodium chloride injections, (D) solution C with preservatives, (E) amino acid and dextrose TPN solution with magnesium sulfate and folic acid, (F) solution E with albumin 6.25 g in 500 ml, (G) amino acid and dextrose TPN solution with calcium gluconate and multivitamins, and (H) solution G with albumin 6.25 g in 500 ml. Each solution was inoculated with 1 X 10(5) bacteria/ml or 1 X 10(3) yeast/ml in 12 serial dilutions using minimum inhibitory concentration (MIC) plates. These were incubated at 37 degrees C for 48 hours, and cultures were visually rated on a scale of 0 (no growth) to 4 (maximal growth). Each culture was repeated for a total of 10 samples. Microbial growth was not affected by the low concentrations of preservatives available from the TPN additives. Undiluted TPN solutions were able to sustain fungal growth only. There was a significant increase in microbial growth in diluted TPN solutions containing albumin for S. aureus, C. albicans, T. glabrata, K. brier, S. marcescans, and E. coli. The presence of vitamins (solution G) impaired the ability of gram-negative bacteria to proliferate, and the addition of albumin (solution H) had no significant effect on the growth characteristics of the organisms in the solution. The presence of albumin had no effect on the growth of S. faecalis or Ps. aeruginosa. The addition of albumin to crystalline amino acid TPN solutions increases the potential of these solutions to support the growth of fungi and bacteria. Hence, it is recommended that albumin be administered separate from amino acid TPN solutions.     

Physical compatibility of neonatal total parenteral nutrient admixtures containing organic calcium and inorganic phosphate salts.

PURPOSE: The compatibility of calcium and phosphate salts in total parenteral nutrient (TPN) admixtures at the highest concentrations recommended for preterm and term infants was studied. METHODS: Particulate matter from eight different macronutrient combinations was measured and counted (range, 1.8-50 mum) by a laser-based, single-particle optical sensing technique. Measurements were performed at four intervals after compounding the formulations under aseptic conditions (within 1 hour of preparation and at 6, 24, and 30 hours) at 23-27 degrees C. The number of particles measuring >or=5, >or=10, and >or=25 microm per milliliter of TPN admixture was recorded. Detailed visual inspections were also performed at these intervals, and pH was measured at the beginning (time 0) and end of the study (30 hours). Precipitated material was characterized by polarized microscopy and infrared spectroscopy. RESULTS: The TPN admixture with the lowest concentration of amino acids (0.5%), as well as the highest pH, resulted in significant growth of particulate matter over time. At 30 hours, the particle growth was accompanied by visible evidence of precipitation, which was confirmed to be dibasic calcium phosphate. Neither significant particle growth nor precipitation was noted in the remaining seven formulations, which had amino acid concentrations of 1-4%. CONCLUSION: Commonly used organic calcium and inorganic phosphate salts in cysteine-added, lipid-free TPN formulations at the highest recommended amounts for neonates were compatible when the amino acid concentration was between 1% and 4% and the dextrose concentration was 5% or 10%. The salts remained compatible for up to 30 hours at a room temperature of up to 27 degrees C. Precipitation of dibasic calcium phosphate occurred with lower amino acid concentrations and higher pH values.     

Stability of vancomycin hydrochloride in 5% dextrose and 0.9% sodium chloride injections

The stability of vancomycin hydrochloride mixed with 5% dextrose and 0.9% sodium chloride injections was studied. Vancomycin hydrochloride powder was mixed with each of the two diluents in final concentrations of 5 mg/mL. Duplicate samples of each admixture were divided into four parts and stored at 24 degrees C in glass and in plastic i.v. bags for 17 days and at 5 degrees C and -10 degrees C in glass for 63 days. To additional samples, hydrochloric acid or phosphate buffer was added; these were stored at 24 degrees C for 17 days. At various storage times, clarity and pH of the samples were recorded and vancomycin concentrations were measured in triplicate by high-performance liquid chromatography. Except for the buffered samples, all solutions remained clear and pH was unchanged. Vancomycin concentrations decreased less than 6% during 17 days at room temperature. In the refrigerated and frozen samples, vancomycin concentrations decreased less than 1% throughout the study. Vancomycin hydrochloride is stable in admixtures with 5% dextrose injection and 0.9% sodium chloride injection for 17 days at 24 degrees C and for 63 days at 5 degrees C and -10 degrees C.     

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)     

The macroanionic activity of heparins in the presence of dextrose and calcium ion

The effect of dextrose on heparin was investigated using the heparin-azur A interaction as a measure of macroanionic activity. Dextrose solutions did not diminish heparin-azur A metachromasia but prior autoclaving of the dextrose solution resulted in a slight decrease. When calcium chloride was added to the dextrose (autoclaved or unautoclaved) there was a reduction which was greater than that caused by calcium ion in the absence of dextrose. The effects of calcium ion and dextrose acting together were each concentration - dependent. A low molecular weight fraction (8400) was more susceptible to the effects of calcium in the presence of dextrose than a fraction of mol. wt. 19 000, hence unfractionated heparins with different amounts of various fractions may respond differently to calcium in the presence of dextrose. This has not been considered in earlier studies of the anticoagulant activity of unfractionated heparins in dextrose infusion and could has contributed to reported discrepancies, particularly in view of the variety of test methods used. At present, it is not possible to predict from in vitro tests whether dextrose will modify the in vivo anticoagulant activity of heparin.     

钙片及氨基酸对婴幼儿生长发育的影响

目的 探讨钙片及氨基酸对婴幼儿生长发育的影响.方法 90例生长发育迟缓的患儿,分成A、B和C三组.A组不给予药物干预,B组给予口服维D2磷葡钙片,C组给予维D2磷葡钙片加复方氨基酸颗粒.结果 干预3个月后C组身高平均增长值高于A组.干预3个月后C组体重平均增长值高于A组;干预6个月后C体重平均增长值高于A组和B组,差异有统计学意义（P＜0.01）.结论 维D2磷葡钙片加复方氨基酸颗粒能够较好的促进婴幼儿生长发育.     

In vitro evaluation of the stability of ranitidine hydrochloride in total parenteral nutrient mixtures

The stability of ranitidine hydrochloride in various total parenteral nutrient (TPN) solutions was studied, as well as the effect of ranitidine on the stability of lipid emulsion and amino acids in these solutions. Ranitidine hydrochloride 25 mg/mL was added to each of the following mixtures to make final concentrations of approximately 50 and 100 mg/L: (1) TPN solution containing 4.5% amino acids, 22.7% dextrose, and electrolytes; (2) 10% lipid emulsion; (3) TPN solution containing 3.7% amino acids, 18.5% dextrose, 3.7% lipid emulsion, and electrolytes (all-in-one mixture); and (4) 0.9% sodium chloride injection. Mixtures were tested at room temperature and at 4 degrees C and were either protected from or exposed to fluorescent light. Sampling was done at 0, 12, 24, 36, and 48 hours, and the ranitidine concentration was determined by high-performance liquid chromatography. Samples were also analyzed for lipid particle size distribution and for amino acid content. At 48 hours, the all-in-one mixtures retained 86.0% to 91.4% of the initial ranitidine concentration. With one exception (ranitidine 50 mg/L in 0.9% sodium chloride injection, stored at room temperature and not protected from light), all other solutions retained at least 90% of the initial concentration at 48 hours. No visible changes in color and minimal changes in pH values were noted. There were no important changes in lipid particle-size distribution; 96% of all particles counted from any mixture were smaller than 1.44 microns in diameter at 48 hours. Ranitidine did not have an effect on amino acid concentrations in these mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of retrograde aminophylline administration on calcium and phosphate solubility in neonatal total parenteral nutrient solutions

The effect of retrograde administration of aminophylline injection on calcium and phosphate solubility in neonatal total parenteral nutrient (TPN) solutions was studied. Neonatal TPN solutions containing two amino acids solutions in three concentrations (Travasol 1% and 2% and TrophAmine 2%) were formulated. Calcium and phosphate salts were added to achieve calcium concentrations of 10, 15, 20, 25, 30, or 40 meq/L and phosphorus concentrations of 10, 15, 20, 25, 30, or 40 mmol/L. Samples were inspected visually after 18-24 hours; solutions free of precipitation were then infused through two parallel syringe-pump systems designed to simulate clinical conditions for TPN solution administration to a 1-kg neonate. To one system, a 7.5-mg aminophylline dose was added as a manual retrograde injection; sterile water for injection was added as a manual retrograde injection to the other system. The solutions were inspected throughout a one-hour infusion period for precipitate formation in the i.v. apparatus, and the pH of the effluents was determined. Concurrent aminophylline administration resulted in visible precipitate in all but a few of the solutions tested. The solution containing Travasol 2%, calcium 10 meq/L, and phosphorus 10 mmol/L remained clear, as did the solutions containing TrophAmine 2% and the following concentrations of calcium and phosphorus: calcium 10 meq/L and phosphorus 10, 15, or 20 mmol/L; calcium 15 meq/L and phosphorus 10 or 15 mmol/L; and calcium 20 meq/L and phosphorus 10 or 15 mmol/L. An average increase in pH of 0.63 unit was noted in all solutions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Compatibility of clindamycin phosphate with cefotaxime sodium or netilmicin sulfate in small-volume admixtures

The stability and compatibility of clindamycin phosphate plus either cefotaxime sodium or netilmicin sulfate in small-volume intravenous admixtures were studied. Admixtures containing each drug alone and two-drug admixtures of clindamycin phosphate plus cefotaxime sodium or netilmicin sulfate were prepared in 100 mL of 5% dextrose injection and 0.9% sodium chloride injection in both glass bottles and polyvinyl chloride (PVC) bags. Final concentrations of clindamycin, cefotaxime, and netilmicin were 9, 20, and 3 mg/mL, respectively. All solutions were prepared in duplicate and stored at room temperature (24 +/- 2 degrees C). Samples were visually inspected, tested for pH, and assayed for antibiotic concentration using stability-indicating assays at 0, 1, 4, 8, 16, and 24 hours for admixtures in glass bottles and at 0, 8, and 24 hours for admixtures in PVC bags. No substantial changes in color, clarity, pH, or drug concentration were observed in any of the solutions. Clindamycin phosphate is compatible with cefotaxime sodium or netilmicin sulfate in 5% dextrose and 0.9% sodium chloride injections in glass bottles or PVC bags for 24 hours.     

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 cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions

The stability of cisplatin, iproplatin, carboplatin, and tetraplatin in common intravenous solutions was studied. Admixtures of each drug in each of the following vehicles were prepared in glass containers: 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection (admixtures were prepared in plastic bags also), and 5% dextrose and 0.225% sodium chloride injection. Drug concentrations were monitored for 24 hours using stability-indicating high-performance liquid chromatographic methods. The stability of cisplatin and tetraplatin was related to the chloride ion content of the infusion fluid; when the infusion fluid contained 0.9% sodium chloride, each of these drugs was present at greater than 90% of the original concentration after six hours. The stability of iproplatin was not related to chloride concentration. A slight increase in the decomposition rate of carboplatin was observed in the presence of chloride ion. Carboplatin and iproplatin are stable for 24 hours in all the infusion fluids studied, but carboplatin should not be diluted with solutions containing chloride ions because of possible conversion to cisplatin. Cisplatin is stable for 24 hours in admixtures containing sodium chloride concentrations of 0.3% or greater. Tetraplatin is stable for six hours in admixtures containing sodium chloride concentrations of at least 0.018%.     

Complexation/encapsulation of green tea polyphenols in mixed calcium carbonate and phosphate micro-particles

We used a double-jet mixer to encapsulate water-soluble polyphenols, green tea extract (GTE), with calcium-based inorganic materials. The device mixed calcium chloride solutions with a solution of carbonate and phosphate in the presence of a GTE solution, and formed micro-particles which capture the GTE molecules. The micro-particles were analysed by liquid chromatography coupled to tandem mass spectroscopy to determine the encapsulation yield and loading of the different GTE components. We established correlations between (1) the efficiency of the GTE encapsulation and the composition of the mixed anion solutions and (2) the protonation degree of the ions and the molar ratio of calcium cations and carbonate/phosphate anions. An optimal and reproducible GTE loading of about 40% with an encapsulation yield of 65% was observed for a carbonate/phosphate molar composition of 4?:?1. In addition, our experimental results showed that the process is selective and favours the encapsulation of gallated species which form stronger complexes with calcium cations.