Admixture studies, parenteral

Therefore, admixture studies are performed on parenteral drugs with commonly used intravenous diluents. Studies are performed by preparing admixtures of the drug product with various diluents in an appropriate type of flexible intravenous bag. Initial samples are taken for analysis before the bags are stored in temperature-controlled stability chambers. Subsequent samples may be pulled at 6-, 12-, 24-, 48-, and 72-h time points. The analytical tests commonly performed include visual appearance, pH, and HPLC assay. Degradation products are not commonly tested unless the method has been previously evaluated for specificity and stability-indicating ability with a particular intravenous diluent. This is necessary because there may be differences in the stability profile of the product in its original formulation compared to the admixture solution. Formation of any particulate matter is detected by visual... 

Peroxide formation has also been observed in multivitamin solutions for parenteral nutrition. Lavoie and co-workers [30] have studied the action of light, air, and composition on the stability of multivitamin formulations, and also total parenteral nutrition (TPN) admixtures containing and not containing vitamins and fatty acids. They analyzed the generation of peroxide in multivitamin solutions and in TPN for adults and neonates. The analysis of multivitamin solutions for enteral use revealed the presence of peroxides at the initial opening of the bottle. The levels were higher in Poly-Vi-Sol (vitamin A, Vitamin D, and vitamin C, vitamin Bb riboflavin, and... 

Precipitates can develop in parenteral nutrition admixtures because of a number of factors such as the concentration, pH, and phosphate content of the amino acid solutions, the calcium and phosphorus additives, the order of mixing, or the mixing process. The consequences can be serious. In one cohort study of hospitalized patients who received peripheral parenteral nutrition, a subgroup developed unexplained chest pain, dyspnea, cardiopulmonary arrest, or new interstitial infiltrates on chest radiograph. A change in the amino acid source of a parenteral nutrition mixture was associated with respiratory adverse events that ranged from interstitial infiltrates to sudden death. The events apparently resulted from infusion of calcium phosphate precipitate in an opaque admixture, and the deposition of the crystals in the pulmonary microvasculature (147). 

A study in 10 patients undergoing bone-marrow transplantation and given isocaloric and isonitrogenous parenteral nutrition with or without lipids found that ciclosporin pharmacokinetics are not affected by lipid-enriched admixtures. ... 

---