Heat Treatment of Poloxamer-Stabilized Triglyceride Nanodispersions: Effects and Underlying Mechanism.

Lipid nanoemulsions are being investigated for the parenteral administration of poorly soluble drugs. A narrow particle size distribution in these formulations is a prerequisite for meaningful research and safe administration to patients. Autoclaving a poloxamer-stabilized trimyristin nanoemulsion resulted in moderate particle growth and a strong decrease in particle size distribution width ( Göke , K. ; Roese , E. ; Arnold , A. ; Kuntsche , J. ; Bunjes , H. Mol. Pharmaceutics 2016 , 13 , 3187 . ). In this work, the critical parameters for such a change upon autoclaving poloxamer 188-stabilized lipid nanodispersions were investigated to elucidate the underlying mechanism. Nanodispersions of triglycerides with esterified fatty acid chain lengths from C8 to C18 were treated at different temperatures and for varying durations. The influence of a decrease in poloxamer 188's cloud point was tested by adding potassium chloride to the dispersions prior to autoclaving. The influence of poloxamer 188 concentration and of the type of emulsifier was investigated. The change in particle size and particle size distribution width upon heat treatment was analyzed by dynamic or static light scattering or differential scanning calorimetry. A short esterified fatty acid chain length of the triglycerides, high temperatures, and the addition of potassium chloride were key factors for particle growth up to emulsion break up, whereas the cloud point of poloxamer 188 was irrelevant. Sodium dodecyl sulfate and sucrose laurate had negative effects on emulsion stability during autoclaving. It was concluded that the increase in particle size and the decrease in particle size distribution widths upon heat treatment resulted from heat-accelerated Ostwald ripening and not from a coalescence-based process.