Physicochemical stability of two types of intravenous lipid emulsion as total nutrient admixtures.
BACKGROUND
Recent data have demonstrated that total nutrient admixtures (TNAs) are unstable when the percentage of fat (PFAT) globules >5 microm in diameter constitute >0.4% of the total fat present and therefore can be considered pharmaceutically unfit for human administration.


METHODS
We studied five nutritionally balanced TNAs using two different products of different oil composition designed to feed adult patients weighing 40 to 80 kg in 10 kg increments, which were given in final volumes equal to 25 mL/kg. Final concentrations of amino acids, dextrose, and lipids were held constant for each weight level. To provide cationic stress within clinical limits, calcium and magnesium were given in amounts equal to three times the usual daily dose, at 15 mmol each. Five TNAs were made in duplicate and for each product (n = 20) and studied over 5 days. Lipid droplet counts were determined by laser light extinction and conducted at five intervals; immediately after preparation at time 1 (T1), after 4 days at 4 degrees C +/- 2 degrees C (T2), and then at 6 (T3), 24 (T4), and 30 (T5) hours during storage at 25 degrees C +/- 1 degree C. At T3, a simulated patient infusion, set at a rate to deliver the entire volume over the next 24 hours, was begun. Samples taken at T3, T4, and T5, equal to 0, 18, and 24 hours, respectively, of the simulated patient infusion, were collected from the terminal infusion port of the i.v. administration set. Mean particle size (MPS) was determined by dynamic light scatter at T1, T3, and T5. Dependent variable analyses included the PFAT globules > 1.75 and 5 microm and MPS. A repeated-measure two-way ANOVA assessing treatment and time was performed.


RESULTS
The MCT/LCT-based TNAs had significantly fewer enlarged fat globules >1.75 microm (p < .0001) and >5 microm (p = .046), and smaller MPS (p < .0001) than TNAs made with the pure LCT emulsion. Of the 20 TNAs studied, 4 demonstrated visible evidence of instability (ie, heavy creaming or free oil), each occurring on day 5 only with the 70- and 80-kg LCT-based TNAs, and no evidence of instability with admixtures prepared from MCT/LCT lipid emulsions (chi2 analysis: p < .05).


CONCLUSIONS
Because the final macronutrient concentrations were held constant, the instability seen with the LCT-based TNAs of higher volumes may result from dilution of the electrolyte concentrations that unfavorably alters the electrical double layer and irreversibly commits the emulsion to an unstable state. The greater physicochemical stability achieved with the MCT/LCT-based TNAs, in turn, likely results from the smaller lipid droplet sizes, which may be an inherent property of MCTs.
Driscoll
D F
DF
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Bacon
M N
MN
Bistrian
B R
BR
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004338:Drug Combinations; D004355:Drug Stability; D005217:Fat Emulsions, Intravenous / Q000737:chemistry*; D006801:Humans; D010289:Parenteral Nutrition, Total; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D013012:Sorbitol / Q000737:chemistry
D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; C008288:Lipofundin; D013012:Sorbitol