Physicochemical stability of lipid injectable emulsions: correlating changes in large globule distributions with...

Area of Science:

• Pharmaceutical Sciences
• Colloid and Surface Chemistry
• Drug Delivery Systems

Background:

• Lipid injectable emulsions (LIEs) are crucial for parenteral nutrition and drug delivery.
• Emulsion stability is critical for safety and efficacy, yet predicting instability remains challenging.
• Current methods like single particle optical sensing (SPOS) have limitations in assessing long-term stability.

Purpose of the Study:

• To investigate the impact of lipid type, electrolyte conditions, and pH on the stability of lipid injectable emulsions.
• To evaluate the correlation between single particle optical sensing (SPOS) measurements, specifically PFAT5, and emulsion phase separation.
• To propose an improved method for assessing emulsion stability.

Main Methods:

• Characterization of 21 lipid injectable emulsions with varying lipid types, electrolytes, and pH levels (7.0, 4.75, 2.5).
• Assessment of phase separation instability using visual inspection within 98 hours.
• Analysis of particle size distribution using single particle optical sensing (SPOS) over time.
• Logistic regression analysis to correlate PFAT5 and PFATX values with instability.

Main Results:

• Seven out of 21 conditions exhibited phase separation instability within 98 hours.
• Instability was primarily driven by electrolyte type and pH, not lipid type.
• Single-point SPOS measurements (PFAT5) at 1 hour did not correlate with instability.
• Later time PFAT5 measurements and PFATX (2-10 microm) showed improved correlation with emulsion instability.
• Cracking phenomena were observed and were independent of lipid type.

Conclusions:

• Electrolyte composition and pH are critical factors influencing lipid injectable emulsion stability.
• Single-point SPOS measurements have limitations for predicting emulsion instability.
• An alternative limit test based on the rate of change in large globule counts is proposed to overcome deficiencies in the current USP Chapter 729 PFAT5 test.