Driscoll David F, Ling Pei-Ra, Bistrian Bruce R
Department of Medicine, Division of Clinical Nutrition and Nutrition/Infection Laboratory, B. I. Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
JPEN J Parenter Enteral Nutr. 2007 Mar-Apr;31(2):148-53. doi: 10.1177/0148607107031002148.
The United States Pharmacopeia (USP) has proposed large-globule-size limits to ensure the physical stability of lipid injectable emulsions, expressed as the percent fat >5 microm, or PFAT(5), not exceeding 0.05%. Visibly obvious phase separation as free oil has been shown to occur in some samples if PFAT(5) is >0.4%. We recently found that lipids, newly packaged in plastic (P), exceed the proposed USP limits and seem to produce less stable total nutrient admixtures compared with those made from conventional glass (G), which do meet proposed USP standards. We tested the possible stability differences between 20% lipid injectable emulsions in either P or G in a simulated neonatal syringe infusion study.
Eighteen individual syringes were prepared from each 20% lipid injectable emulsion product (n = 36) and attached to a syringe pump set at an infusion rate of 0.5 mL/hour. The starting PFAT(5) levels were measured at time 0 and after 24 hours of infusion, using a laser-based light obscuration technique as described by the USP Chapter <729>. The data were assessed by a 2-way analysis of variance (ANOVA) with Container (G vs P) and Time as the independent variables and PFAT as the dependent variable.
At time 0, the starting PFAT(5) level for lipids packaged in G was 0.006% +/- 0.001% vs 0.162% +/- 0.026% for P, whereas at the end of the infusion they were 0.013% +/- 0.003% and 0.328% +/- 0.046%, respectively. Significant differences were noted overall between groups for Container, Time, and Container-Time interaction (all p < .001). Bonferroni tests showed significant differences in PFAT(5) levels between Containers at time 0 (T-0; p < .001) and T-0 vs T-24 for P-based lipids (p < .001), whereas no such differences were noted for Time for the G-based lipids. Similar results were noted for PFAT(10) levels.
We confirm that presently available lipid injectable emulsions packaged in newly introduced plastic containers exceed the proposed USP <729> PFAT(5) limits and subsequently become significantly less stable during a simulated syringe-based infusion. Although modest growth (p = NS) in large-diameter fat globules was observed for the glass-based lipids, they remained within proposed USP globule size limits throughout the study. Glass-based lipids seem to be a more stable dosage form and potentially a safer way to deliver lipids via syringe infusion to critically ill neonates.
美国药典（USP）已提出大颗粒尺寸限制，以确保脂质注射乳剂的物理稳定性，以脂肪含量>5微米的百分比（PFAT(5)）表示，不超过0.05%。如果PFAT(5)>0.4%，已证明一些样品中会出现明显的相分离，即游离油。我们最近发现，新包装在塑料（P）中的脂质超过了USP提出的限制，与符合USP标准的传统玻璃（G）制成的脂质相比，似乎产生的全营养混合液稳定性更低。我们在一项模拟新生儿注射器输注研究中测试了P或G包装的20%脂质注射乳剂之间可能存在的稳定性差异。
从每种20%脂质注射乳剂产品中制备18个单独的注射器（n = 36），并连接到设置为0.5 mL/小时输注速率的注射泵上。使用USP第<729>章所述的基于激光的光散射技术，在时间0和输注24小时后测量初始PFAT(5)水平。数据通过双向方差分析（ANOVA）进行评估，其中容器（G与P）和时间为自变量，PFAT为因变量。
在时间0时，G包装的脂质的初始PFAT(5)水平为0.006%±0.001%，而P包装的脂质为0.162%±0.026%，而在输注结束时，它们分别为0.013%±0.003%和0.328%±0.046%。在容器、时间和容器-时间交互作用方面，各组之间总体上存在显著差异（所有p <.001）。Bonferroni检验显示，在时间0（T-0；p <.001）时，容器之间的PFAT(5)水平存在显著差异，对于基于P的脂质，T-0与T-24之间也存在显著差异（p <.001），而对于基于G的脂质，时间方面未发现此类差异。PFAT(10)水平也有类似结果。
我们证实，目前包装在新引入的塑料容器中的脂质注射乳剂超过了USP <729>提出的PFAT(5)限制，因此在模拟注射器输注过程中稳定性显著降低。尽管观察到基于玻璃的脂质的大直径脂肪球有适度增长（p =无显著性差异），但在整个研究过程中它们仍保持在USP提出的球粒尺寸限制范围内。基于玻璃包装的脂质似乎是一种更稳定的剂型，并且可能是通过注射器输注向重症新生儿输送脂质的更安全方式。
