Administration of parenteral products

Whereas the compounding and administration of parenteral products and intravenous admixtures continues to be a vital and important component in the care of hospitalized and home health care patients, there is continued interest in easing the preparation, storage, and administration of these products with respect to controlling contamination of the finished product and protecting the health care providers from needlestick injuries. It is estimated that more than... 

Table 14.1 Formulation Properties and Terms Concerning Administration of Parenteral Products Essential for the Photochemical Stability...

Historically, the rabbit pyrogen test constituted the most widely used method. This entails parenteral administration of the product to a group of healthy rabbits, with subsequent monitoring of rabbit temperature using rectal probes. Increased rabbit temperature above a certain point suggests the presence of pyrogenic substances. The basic rabbit method, as outlined in the European Pharmacopoeia, entails initial administration of the product to three rabbits. The product is considered to have passed the test if the total (summed) increase of the temperature of all three animals is less than 1.15 °C. If the total increase recorded is greater than 2.65 °C then the product has failed. However, if the response observed falls between these two limits... 

Parenteral administration of contaminated product would likely lead to the establishment of a severe infection in the recipient patient. 

Neitlich, H.W., and Pless, J.E. Effect on Man of Parenteral Administration of A Production-line Mixture of Isomers 2 and 4,... 

The routes of administration for parenteral products are shown in Fig. 1. The most commonly used routes... 

Fig. 1 Routes of parenteral administration. The following represent the most commonly used routes of administration for parenteral products (A) intraperitoneal (B) intravenous (C) intramuscular (D) subcutaneous and (E) intradermal.

Since the introduction of parenteral nutrition in hospital care the potential microbiological risks associated with the manufacture, preparation, and administration of these products have abated but not disappeared (133,152). Fatal infectious complications still occur. The parenteral nutrition mixture is a good growth medium for microorganisms, more conducive to microbial growth than glucose or amino acid solutions. Storage of mixtures... 

Supportive measures, including administration of blood products, parenteral fluid, and electrolytes, are recommended. Removal of the seeds from the gastrointestinal tract can be done with charcoal. Whole bowel irrigation may also be considered after a dose of charcoal for patients with voluminous ingestions. Alkalinization of the urine with sodium bicarbonate has been recommended for the prevention of hemoglobin precipitates in the renal tubules. 

Parenteral products, by nature of the fact that they are administered directly into the human bloodstream, bypass virtually all of the body s inherent barriers to infection. They are also riskier than oral solid dosage products because there is a higher propensity for improper administration of injectable products as well as the reality of patients with compromised immune systems, among other things. It is for these reasons that the utmost attention to—and assurance of—quality, safety, and efficacy are required to properly manufacture the parenteral dosage form. 

The formulation of parenteral products involves careful consideration of the proposed route of administration and the volume of the injection. Injections are administered to the body by many routes into various layers of the skin, the subcutaneous and muscle tissue, into arteries or veins, into or around the spinal cord, or directly into various organs (e.g., the heart or the eye). The volume to be injected can range from microliters, typically diagnostic agents administered intradermally or insulin administered subcutaneously, to several liters administered intravenously as infusions. The route of administration and the volume to be injected affect the composition of the formulation. 

The choice of elastomer has the greatest effect on a formulation. The most common elastomers that can be used for closures for injectable products are given in Table 12.5. Of these elastomers, natural rubber, synthetic polyisoprene, butyl, chlorobutyl and bromobutyl rubber are typically used for the manufacture of rubber closures and stoppers used in the packaging and administration of parenterals. 

Filled containers of parenteral products for administration to humans should be inspected individually. 

Sterilization is an essential stage in the processing of aity product destined for parenteral administration, or for contact with broken skin, mucosal surfaces or internal organs, where the threat of infection exists, hi addition, the sterilization of microbiological materials, soiled dressings and other contaminated items is necessary to minimize the health hazard associated with these articles. 

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