Stability and compatibility of parenteral nutirtion Staffan Bark, MD, PhD Backgatan 11, 62155 Visby, Sweden Email: staffan@fresenius-kabi.com Stability can be divided into chemical stability and physical stability. An admixture for parenteral nutrition (PN) is exposed to many challenges. The constituents included should not react with each other and form new molecules and they should not degrade during manufacturing and storage. Heat sterilization is another challenge. As an example, glutamine is unstable when heated to appropriate temperature and degrades by forming glutamate and pyro-glutamate. The two glutamine-containing dipeptides available on the market are on the other hand very heat stable. Incompatibilities between molecules may also result in precipitation and thus formation of particles. Calcium and phosphate can create problems in this context if the mixing is done in the wrong way. Fat emulsions are other parts of PN that must be considered. An emulsion consists by definition of two ingredients that cannot be dissolved but anyway exist together in two different phases. The most common type is lipid emulsion with a lipid phase and a water phase. The particles of the emulsion are kept apart by electronic charges. The spherical particles of a lipid emulsion are covered by the negatively charged phospholipid molecules facing the outer "water world" thus creating a hydrophilic environment. The inner part of the surrounding shell contains the fatty acids of the PL molecule and forms the lipophilic side facing the lipid containing inner content of the particle. The negatively charged particle repels all other neighbor-particles. If the PN admixture is challenged by an added solution that may neutralize the negative charges, the emulsion stability is at risk. Therefore, there are restrictions to add drugs or other things that haven't been tested for stability. It has however been commonly accepted to add small amounts of heparin to admixtures in order to diminish the risk for thrombophlebitis. The amount shold not exceed 1000 IU per liter of the admixture. Some people add also hydrocortisone for the same purpose. Other drugs should be avoided. Even piggy-back infusion of a drug with un-known compatibility with the nutrition admixture in a Y-connection should be avoided since precipitation may appear quickly already in the tubing before reaching the blood stream. Additives should be added as close as possible to the start of infusion. If the additives are handled in a hospital pharmacy with proper equipment, some additives (according to the manufacturer's recommendations) may be mixed up to a month in advance but then admixture must be stored in refrigerator. From "The 11th PENSA Congress" October 1-4, 2005, Sheraton Grande Walkerhill Hotel, Seoul, Korea. Page: 107