Autoclaving behavior of trimyristin nanoemulsions stabilized with different poloxamers

Abstract

Lipid nanoemulsions are being investigated as carrier systems for the parenteral administration of poorly soluble drugs. Defined particle sizes, narrow particle size distributions, and sterility are prerequisites for the safe administration of such formulations to patients. In the current study, autoclaving of such formulations was performed to achieve both, sterility and a narrow particle size distribution. The high temperatures applied might, however, have an impact on emulsion stability. The influence of various types of poloxamer (Pol) on the formation of trimyristin (TM) nanoemulsions with around 100 nm (± 2 nm) mean particle size, as well as on the physical stability, particle size and particle size distribution changes during autoclaving of the emulsions was investigated. Higher homogenization pressures were required to achieve the target particle size in emulsion formulations stabilized with poloxamers of larger molecular size. A correlation between the autoclavability of the formulations and the cloud point of the respective poloxamer used for emulsion stabilization was observed. A PEO content of 70 % or above within the poloxamer molecule was needed to achieve stable nanoemulsions after autoclaving. In stable emulsions, Ostwald ripening occurred during autoclaving, indicated by particle size growth and narrowing of the particle size distribution, which was accompanied by changes in the melting behavior of the recrystallized emulsion droplets. Autoclaving of TM nanoemulsions stabilized with Pol 108, 188, 237, 238, 338 and 407 yielded systems with particularly well-defined particle sizes and narrow particle size distributions.