Assessment of the Physicochemical Stability of All‐in‐One Parenteral Emulsions for Neonates According to USP Specifications

Abstract

The presence of calcium destabilized the admixtures, while the use of different commercial ingredients altered the admixtures' characteristics. Only 1 batch of the AIO admixtures studied was found to be compliant with USP <729> standards.

Development and evaluation of a test program for Y-site compatibility testing of total parenteral nutrition and intravenous drugs

“…Assessment of possible precipitates are typically performed by one or more of the following approaches: visual examination with Tyndall light [ 11 , 12 , 24 , 29 ] or other visual examination methods [ 13 , 27 , 30 , 31 ], turbidimetric measurements [ 26 , 29 ], colorimetric measurement [ 13 ], light obscuration (LO) [ 13 , 31 ], dynamic light scattering (DLS) [ 27 ], microscopy [ 32 ] and pH-measurements [ 30 – 32 ]. Various methods have also been used to investigate parenteral emulsion stability: visual observation with [ 12 ] or without a centrifugation step [ 13 , 25 , 28 , 32 – 35 ], determination of zeta potential [ 25 , 28 , 34 , 36 – 38 ], measurement of dynamic surface tension [ 37 ], measurement of peroxide levels [ 28 ], pH-measurements [ 13 , 25 , 28 , 33 – 35 ] and different droplet size measurement techniques. The latter techniques are e.g.…”

Assessment of the Physicochemical Stability of All‐in‐One Parenteral Emulsions for Neonates According to USP Specifications, Athanasiou et al

“…Moreover, in studies simulating the infusion of stable (PFAT5 <0.05%) vs unstable (PFAT5 >0.05%) lipid emulsions via syringe delivery, the PFAT5 level in unstable emulsions grew by more than a factor of 10 in 24 hours, whereas over the same period in the stable lipid emulsions, the PFAT5 level doubled but still remained <0.05% 8 . It should be noted that these emulsions were not diluted (ie, as all‐in‐one admixtures) as in the Athanasiou et al 1 study but were 20% w/v soybean oil–in–water injectable emulsions that were extemporaneously prepared in syringes, as performed in our neonatal intensive care unit (ICU), and is standard practice in United States. We have shown in some pediatric formulas (n = 3) that all‐in‐one admixtures made from lipid emulsions that contain medium‐chain triglycerides can be stable for up to 48 hours via PFAT5 <0.05% measured by light extinction with a single‐particle optical sensing (LE/SPOS) technique, but the sample size is too small to recommend all‐in‐one admixtures routinely in this patient population 9 .…”

“…In this issue of the Journal of Parenteral and Enteral Nutrition ( JPEN ), Athanasiou and colleagues 1 describe the method to assess the stability of all‐in‐one parenteral nutrition admixtures intended for neonates according to the standards of the United States Pharmacopeia (USP, Chapter <729>) that includes Method I, which states, “The intensity‐weighted mean droplet diameter (MDD) for lipid injectable emulsions must be less than 500 nm or 0.5 µm, irrespective of the concentration of the dispersed phase” (p. 362) and Method II, which states, “The volume‐weighted, large‐diameter fat globule limits of the dispersed phase, expressed as the percentage of fat residing in globules larger than 5 µm (PFAT5) for a given lipid injectable emulsion, must not exceed 0.05%” (p. 363) 2 . Compliance with USP <729> necessitates performing these 2 methods in 2 stages to meet pharmacopeial requirements.…”

“…In their report, Athanasiou and colleagues 1 describe in the Materials and Methods section that the physicochemical characterization to assess stability of the emulsion was accomplished according to USP <729> and that the PFAT5 assessment was determined by laser diffraction (LD). The PFAT5 values are not reported in Table 3 of their study, but compliance is assigned an “A” for within acceptable limits or “R” rejected admixtures, but only the actual numerical values are valid in such a study.…”

Physicochemical Stability and Sterility of Standard Parenteral Nutrition Solutions and Simulated Y‐Site Admixtures for Neonates

“…There is lack of consensus on the parameters to be determined when evaluating stability of PN solutions. Our selection was based on previous neonatal PN stability studies 13,20 and relevant causes of PN instability and incompatibility stated in the Spanish Consensus on Compounding of PN admixtures. 19 The physicochemical parameters, and their corresponding methods, used to assess stability of standard ILE-free PN solutions were the following:…”