Assessment of ascorbic acid stability in different multilayered parenteral nutrition bags: Critical influence of the bag wall material

Background: The recent development of multilayered bags has minimized ascorbic acid oxidation in parenteral nutrition (PN) admixtures. However, the gas-barrier property of multilayered bags depends on their plastic material. This study compared ascorbic acid stability in different multilayered bags under experimental conditions. Methods: Oxygen permeability of a newly developed 6-layered bag (6-L) was compared with a highly mechanical-resistant 3-layered bag (3-L-R) and a highly flexible 3-layered bag (3-L-F) using gas chromatography. Ascorbic acid stability was assessed by iodine titration in bags filled with 2.5 L H2O and 40 g carbohydrates after setting residual O-2 content at <= 1 or >= 5 ppm. The effect of storage at 4 degrees C, 21 degrees C, and 40 degrees C on ascorbic acid stability was assessed over 48 hours in a complete PN admixture (ie, 330 g carbohydrates, 100 g lipids, 96 g amino acids and trace elements) using high-pressure liquid chromatography. Results: Oxygen permeability was markedly reduced in 6-L bags (0.5 mL O-2/m(2)/d) compared with 3-L-R (150 mL O-2/m(2)/d) and 3-L-F (1500 mL O-2/m(2)/d). Accordingly, ascorbic acid was more stable in 6-L bags (half-life [T-1/2] = 16 days up to 40 degrees C) than in 3-L-R (T-1/2 = 9 days at 4 degrees C, 47 hours at 21 degrees C and 29 hours at 40 degrees C) and 3-L-F (T-1/2 = 15 hours at 4 degrees C, 10 hours at 21 degrees C, and 6 hours at 40 degrees C). During the first 6 hours after PN admixture compounding, an additive ascorbic acid loss of 4.6 +/- 0.5 mg/L/ppm O-2 occurred because of residual O-2 in the bag. Conclusions: The new combination of plastic layers and careful O-2 monitoring during the filling process allowed near to complete prevention of ascorbic acid degradation in multilayered PN bags during 48 hours, regardless of the storage temperature.