Total parenteral nutrition formulations

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... 

In parenteral formulations, medium-chain triglycerides have similarly been used in the production of emulsions, solutions, or suspensions intended for intravenous administration. Medium-chain triglycerides have been particularly investigated for their use in total parenteral nutrition (TPN) regimens in combination with long-chain triglycerides. ... 

Additionally, sodium bicarbonate is used in solutions as a buffering agent for erythromycin, lidocaine, local anesthetic solutions, and total parenteral nutrition (TPN) solutions. In some parenteral formulations, e.g., niacin, sodium bicarbonate is used to produce a sodium salt of the active ingredient that has enhanced solubility. Sodium bicarbonate has also been used as a freeze-drying stabilizer and in toothpastes. 

In pharmaceutical preparations, soybean oil emulsions are primarily used as a fat source in total parenteral nutrition (TPN) regimens. Although other oils, such as peanut oil, have been used for this purpose, soybean oil is now preferred because it is associated with fewer adverse reactions. Emulsions containing soybean oil have also been used as vehicles for the oral and intravenous administration of drugs drug substances that have been incorporated into such emulsions include amphotericin, " diazepam, retinoids, vitamins, poorly water-soluble steroids, fluorocarbons, and insulin. In addition, soybean oil has been used in the formulation of many drug delivery systems such as liposomes, microspheres, dry emulsions, self-emulsifying systems, and nanoemulsions and nanocapsules. ... 

As stated previously, contaminated products injected directly into the bloodstream or instilled into the eye cause the most serious problems. Intrathecal and epidural injections are potentially hazardous procedures. In practice, epidural injections are frequently given through a bacterial filter. Injectable and ophthalmic solutions are often simple solutions and provide Gram-negative opportunist pathogens with sufficient nutrients to multiply during storage if contaminated, a bioburden of 106 CFU as well as the production of endotoxins should be expected. Total parenteral nutrition fluids, formulated for individual patients ... 

Biotin Deficiency. Relative to many of the vitamins, it is easy to induce a biotin deficiency by feeding volunteers raw egg white. Avidin, a basic protein found in egg white, forms salt linkages with acidic biotin and prevent its transport across the intestinal barrier. Cooked egg white is not a problem. Because biotin is found in the yolk, eating whole raw egg will not induce a deficiency. Deficiencies also were caused in patients on total parenteral nutrition (TPN) because biotin was not included in the early formulations. Symptoms include dermatitis, loss of hair color, and central neurological effects. 

Parenteral emulsions were first introduced to provide an IV source of essential fatty acids and calories. This has developed into the extensive and routine use of products such as Intraplipid, Lipofundin and Liposyn in total parenteral nutrition. There are relatively few commercially available emulsions containing active compounds the only example on the U.S. market is Diprivan Injectable Emulsion, the formulation of which is shown in Table 9.4. Diazepam is also available as an injectable emulsion on the UK market (Diazemuls ). For a more detailed discussion of the issues involved in developing parenteral emulsions, the reader is referred to Collins-Gold et al. (1990). 

Preparations for total parenteral nutrition (TPN) are complex formulations intended for administration by the intravenous route. TPN preparations are formulated as aqueous solutions or hydrophilic (oil-in-water) emulsions they may contain amino acids, carbohydrates, fatty acids, emulsifiers, electrolytes, trace metals, vitamins, and minerals (Hutchinson, 1998 Trissel, 2001). In certain cases, drugs are added to the preparations prior to administration. The environment is thus rather heterogeneous, and the photochemical stability of different components can vary from formulation to formulation and be hard to predict. It is necessary to perform experiments based on studies of the actual composition to obtain correct information concerning photostability of the formulation or components present. 

Emulsions intended for total parenteral nutrition (TPN) are formulated using vegetable or neutral oils as dispersed phase and phospholipids as emulsifier with the objective that they are not recognized as foreign by the body. They can be considered as being artificial chylomicrons and enter the fat metabolism pathway through the adsorption of apolipoproteins and the subsequent action of lipoprotein lipase. 

For intravenous or intramuscular administration, oil-soluble actives can be formulated as an oil-water-emulsion. When administered intravenously it is essential that the droplet size is about the same size as the lipid particles that circulate in the blood, the chylomicrons (0.2-3 pm). A typical emulsion contains 10-20 % soybean oil, 2 % glycerol and 1 % egg lecithin. These emulsions cannot be autoclaved. Coalescence of the droplets of the internal phase is a typical sign of instability. All-in-one total parenteral nutrition admixtures are a typical example for parenterally administered emulsion (compare Sect. 13.9). 

In order to insure maximum safety to the patient, it is strongly recommended that any institution in which intravenous hyperalimentation is practiced should have a designated and qualified hyperalimentation or total parenteral nutrition team. The minimum team should consist of an attending physician who is well versed in nutrition and metabolism, a conscientious and interested house officer or research fellow, a pharmacist trained in aseptic solution formulation, and a technician or nurse. Other members of a complete hyperalimentation team include a nutritionist, clinical pathologist or biochemist, physical therapist, sociologist, and psychiatrist. 

PN should provide a balanced nutritional intake, including macronutrients, micronutrients, and fluid. Macronutrients, including amino acids, dextrose, and intravenous lipid emulsions, are important sources of structural and energy-yielding substrates. A balanced PN formulation includes 10% to 20% of total daily calories from amino acids, 50% to 60% of total daily calories from dextrose, and 20% to 30% of total daily calories from intravenous lipid emulsion. Micronutrients, including electrolytes, vitamins, and trace elements, are required to support essential biochemical reactions. Parenteral... 

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