Physicochemical stability of total nutrient admixtures

Area of Science:

• Parenteral nutrition
• Formulation science
• Physical chemistry

Background:

• Intravenous (i.v.) nutritional emulsions are critical for patients requiring nutritional support.
• Ensuring the stability of these complex admixtures is essential for patient safety and therapeutic efficacy.
• Factors influencing the physical stability of i.v. nutritional emulsions require thorough investigation.

Purpose of the Study:

• To investigate the impact of six independent factors on the stability of i.v. nutritional emulsions.
• To identify specific components that most significantly affect emulsion stability.
• To establish criteria for predicting emulsion instability.

Main Methods:

• Preparation of 45 i.v. nutritional admixtures with varying concentrations of amino acids, glucose, lipid emulsion, and monovalent, divalent, and trivalent cations.
• Stability assessment using particle-size analysis (light obscuration, dynamic light scatter), pH determination, and visual inspection over 30 hours.
• Statistical analysis using multiple stepwise regression to identify significant factors affecting stability.

Main Results:

• Trivalent cation concentration was the sole significant factor impacting emulsion stability (p < 0.00001), explaining ~60% of increased fat particle sizes.
• Emulsions with >0.4% large fat particles (>5 microns) were associated with instability, though visual detection was only 65% reliable.
• Changes in mean globule diameter, cream layer, and pH did not reliably indicate instability.

Conclusions:

• Trivalent cations, specifically from iron dextran, are highly disruptive to lipid-based parenteral nutrient admixtures.
• A threshold of >0.4% large fat particles serves as a key indicator for potential i.v. nutritional emulsion instability.
• Particle-size analysis is a more sensitive method than visual inspection or pH for detecting early signs of emulsion destabilization.