Stability and compatibility assessment techniques for total parenteral nutrition admixtures: setting the bar according to pharmacopeial standards.
OBJECTIVE
The stability and compatibility of total parenteral nutrition mixtures compounded for patients requiring nutritional support is paramount to their safety on intravenous infusion. The most significant pharmaceutical issues associated with mixing total parenteral nutrition formulations affecting their safety involve the stability of lipid-injectable emulsions and the compatibility of calcium and phosphate salts. Methods of analysis for stability and compatibility have varied, and the assessments have mostly been largely qualitative.


RESULTS
Although pharmacopeial standards have been primarily applicable to pharmaceutical manufacturers, recent efforts by the United States Pharmacopeia have been directed at standardizing pharmacy practices involved in the safe mixing of compounded sterile preparations. The adoption of chapter 797 entitled 'Pharmaceutical compounding - sterile preparations' on 1 January 2004 has had a dramatic impact on pharmacy practice in the United States. More recently, the United States Pharmacopeia has also proposed a new chapter 729 entitled 'Globule size distribution in lipid-injectable emulsions', setting specific limits on the sizes and concentrations of lipid droplets in the formulation, which may have implications for all-in-one mixtures. Finally, new efforts are under way to establish limits on the level of acceptable amounts of particulates intrinsically introduced by the manufacturer, and thus may have ramifications for particulates extrinsically introduced or initiated during compounding by the pharmacist.


CONCLUSIONS
With careful monitoring and the development of appropriate pharmacopeial-based specifications that limit the size and concentration of large-diameter fat globules and eliminate the possibility of dibasic calcium phosphate precipitates, improved patient outcomes may be achieved.
Driscoll
David F
DF
Department of Medicine, Division of Clinical Nutrition, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, USA. ddriscol@bidmc.harvard.edu
D004339:Drug Compounding; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D010289:Parenteral Nutrition, Total / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000592:standards*; D012449:Safety; D013997:Time Factors
D004364:Pharmaceutical Preparations