Physicochemical stability of highly concentrated total nutrient admixtures for fluid-restricted patients.

PURPOSE: The physicochemical stability of highly concentrated total nutrient admixtures (TNAs) for fluid-restricted patients was studied. METHODS: Five TNAs made from lipid injectable emulsions (50:50 mixture of medium-chain and long-chain triglycerides) designed to meet the full nutritional needs of adults with body weights of 40-80 kg were chosen. Protein was included in the TNAs at 1.5 g/kg for each body weight and was supplied from a concentrated 16% mixture containing the essential and non-essential amino acids. All admixtures were contained in ethylene vinyl acetate bags and were aseptically prepared. Triplicate preparations of each TNA were investigated over 30 hours at room temperature by dynamic light scattering (DLS) and light extinction with single-particle optical sensing (LE-SPOS). RESULTS: No significant changes in the physicochemical stability of the TNAs were observed by DLS (mean droplet size) or LE-SPOS (large-diameter tail) from time 0 (immediately after compounding) to 30 hours. All TNAs met the mean-droplet-size criteria outlined by USP for 20% lipid injectable emulsions. CONCLUSION: Concentrated TNA formulations made from lipid injectable emulsions were stable for 30 hours at room temperature.

Establishing a stability window for medium- and long-chain-triglyceride lipid-based total nutrient admixtures using USP standards.

PURPOSE: The stability window of medium-chain triglyceride (MCT) and long-chain-triglyceride (LCT) lipid-based total nutrient admixtures (TNAs) was studied. METHODS: Sixteen different admixtures were selected for study. Of these, eight base macronutrient concentrations representing low and high concentrations were selected, along with low and high concentrations of electrolytes. All TNAs studied contained 2 mg of elemental iron as part of the trace-element formulation, an amount previously shown to produce unstable TNAs with pure LCT-based lipid injectable emulsions. All admixtures were prepared in triplicate and analyzed over five time intervals: time 1 (immediately after preparation), time 2 (after four days of storage at 6 +/- 2 degrees C), and times 3, 4, and 5, corresponding to 6, 24, and 30 hours of storage at 25 +/- 2 degrees C, respectively, after time 2. Stability was measured by comparing results with USP standards for fat globule size in lipid injectable emulsions. RESULTS: A total of 48 admixtures were studied. Samples at each time interval showed an inconsistent but general increase in the number of globules with a diameter of >1.8 microm over time. All admixtures met both the proposed pharmacopoeial criteria for stability with respect to mean droplet size and volume-weighted proportion of fat globules with a diameter of >5 microm. CONCLUSION: A wide range of macronutrients and micronutrients were tested in a series of MCT-LCT-based TNAs and found to be stable. The use of MCTs and LCTs in lipid injectable emulsions confers greater stability to TNAs than has been achieved with pure LCT-based formulations.

Lipid globule size in total nutrient admixtures prepared in three-chamber plastic bags.

PURPOSE: The stability of injectable lipid emulsions in three-chamber plastic (3CP) bags, applying the globule-size limits established by United States Pharmacopeia ( USP ) chapter 729, was studied. METHODS: A total of five premixed total nutrient admixture (TNA) products packaged in 3CP bags from two different lipid manufacturers containing either 20% soybean oil or a mixture of soybean oil and medium-chain-triglyceride oil as injectable lipid emulsions were tested. Two low-osmolarity 3CP bags and three high-osmolarity 3CP bags were studied. All products were tested with the addition of trace elements and multivitamins. All additive conditions (with and without electrolytes) were tested in triplicate at time 0 (immediately after mixing) and at 6, 24, 30, and 48 hours after mixing; the bags were stored at 24-26 degrees C. All additives were equally distributed in each bag for comparative testing, applying both globule sizing methods outlined in USP chapter 729. RESULTS: Of the bags tested, all bags from one manufacturer were coarse emulsions, showing signs of significant growth in the large-diameter tail when mixed as a TNA formulation and failing the limits set by method II of USP chapter 729 from the outset and throughout the study, while the bags from the other manufacturer were fine emulsions and met these limits. Of the bags that failed, significant instability was noted in one series containing additional electrolytes. CONCLUSION: Injectable lipid emulsions provided in 3CP bags that did not meet the globule-size limits of USP chapter 729 produced coarser TNA formulations than emulsions that met the USP limits.

Physical assessments of lipid injectable emulsions via microscopy: a comparison to methods proposed in United States pharmacopeia chapter 729.

In confirming the stability of lipid injectable emulsions, the United States Pharmacopeia has recently recommended that light scattering be used to determine the mean droplet size (i.e., fineness of the dispersion), and light obscuration or light extinction be used to quantify the extent of the large-diameter tail (i.e., coarseness of the dispersion). In confirming the results obtained by these two methods, the usefulness of a third method, differential interference contrast microscopy using an oil immersion technique was investigated. The physical stabilities of 95 different formulations made from 20% w/v lipid emulsions were evaluated by all three methods. A wide spectrum of globule-size distributions was investigated, measured by light obscuration and expressed as the volume-weighted percent of fat greater than 5 micrometers (PFAT5) from very fine (0.001%) to very coarse (0.596%) formulations. The responses obtained by the light scattering method did not reflect the values for the large-diameter tail (i.e., coalescence) seen with the less stable emulsions, whereas these differences were detectable using the differential interference contrast microscopy technique. It was concluded that differential interference contrast microscopy provides complementary data about the physical stability of lipid injectable emulsions and can be applied as a confirmatory evaluation to the methods proposed in United States Pharmacopeia Chapter 729.