Parenteral nutrition formulation

Lecithins are mainly used in pharmaceutical products as dispersing, emulsifying, and stabilizing agents and are included in intramuscular and intravenous injections, parenteral nutrition formulations, and topical products such as creams and ointments. 

Lecithins are also used in suppository bases, to reduce the brittleness of suppositories, and have been investigated for their absorption-enhancing properties in an intranasal insulin formulation. Lecithins are also commonly used as a component of enteral and parenteral nutrition formulations. 

The actual aluminium contents in 40 neonatal parenteral nutrition solutions and 16 component products used in parenteral nutrition formulations have been determined and compared with the calculated amounts from manufacturers product labels, and ascertain whether the actual aluminium exposure exceeds the FDA recommended maximum [14 ]. The measured and calculated aluminium concentrations exceeded the FDA recommended safe... 

Parenteral nutrition formulations provide nutritive support for patients who are not able, not allowed or not willing to eat for a critical period of time. Indications for parenteral nutrition include pre- and postoperative periods of major surgery or trauma, severe obstruction of the gut (e.g. by tumours), severe motility disorders (e.g. ileus), severely impaired absorption capacity (e.g. short bowel syndrome, mucositis in stem cell transplantation patients). Parenteral... 

FIGURE 3 Arsenic level in substances used in formulations for parenteral nutrition [16]. 

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... 

Typical solid lipids used are glycerides and/or fatty acids, and may constitute 30% of the formulation. These are from the same family of lipids found in parenteral nutrition emulsions, such as Intralipid, which have been successfully administered intravenously for several decades. Typical excipients are Dynasan 112, composed of short chain fatty acids, Compritol, lecithin, used as an emulsifier, and surfactants such as polysorbate 80, polaxamer 188, PVP, bile salts such as sodium glycocholate, and Span 85. Water can be replaced with oils or PEG 600 to yield dispersions which can be filled into soft gelatin capsules. 

Some copper compounds have been used therapeutically in the past. Small quantities of copper salts enhance the physiological utilization of iron and are thus often present in hemopoietic formulations. Copper chloride and copper sulfate are used in parenteral nutrition solutions. The artificial radioactive copper isotope Cu has been used in mineral metabolic studies. Excess accumulation of copper can occur due to an abnormality of ceruloplasmin and causes Wilson s disease and Menkes disease, which are both characterized by copper accumulation (SEDA-22, 244) (9). 

Manganese is often present in mineral supplements, in hemopoietic formulations, and in some solutions for parenteral nutrition. Trace elements are required in patients receiving long-term parenteral nutrition (1), and the use of manganese has been reviewed (2). 

Calcium is normally considered to be safe in parenteral nutrition, and relatively high quantities are often included in neonatal and pediatric formulations. However, there is a risk of hjrpercalciuria. The pathogenesis of hjrpercal-ciuria is not readily explicable on the basis of endocrine or metabolic effects, but it has been postulated to be due to excessive calcium or vitamin D intake or aluminium overload. 

Iron is an essential element in nutrition, and its inclusion in any long-term parenteral nutrition regimen should be mandatory. However, it is not included in all trace element formulations, although this varies from country to country most European products include 20 pmol of iron in trace element formulations. While it might be considered unnecessary to include iron as a daily supplement, because of safety and pharmaceutical considerations, there is ample evidence that the use of iron-containing trace element formulations is both safe and efficacious, with no associated adverse effects. 

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. ... 

The chapter should allow an appreciation of the factors leading to emulsion stability and physical instability, including flocculation and coalescence. Approaches to the formulation of emulsions to provide vehicles for drug delivery and parenteral nutrition (the main uses in pharmacy) should be understood. 

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 nutrition (PN) solutions may be appropriately formulated for administration by peripheral or central venous access. 

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). 

Aqueous parenteral preparations can contain trace amounts of heavy metal ions in concentrations sufficient to catalyze oxidative reactions. Aqueous parenterals are produced with the use of Water for injection, which complies with the limit test for heavy metals (European Pharmacopoeia, 2002). This is, however, no guarantee for exclusion of metal ions. Heavy metal contamination brought into the formulation by excipients is also a problem, especially for sugars, phosphate, and citrate (Nema et al., 2002). Heavy metals may also be extracted from the container by the preparation (European Pharmacopoeia, 2002 see Section 14.3). Moreover, trace elements like zinc, copper, manganese, and chromium constitute important components in several parenteral nutrition formulas (Trissel, 2001). 

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. 

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