Critical steps during the prilling process of molten lipids: Main stumbling blocks due to pharmaceutical excipient properties.

Prilling by ultrasonic jet break-up is an efficient process to produce perfectly spherical microparticles homogeneous in size. However, the material properties could affect the manufacturability and the final product properties especially with lipid-based excipients which often exhibit complex structural properties. This work presents the characterisation of six lipid-based excipients differing by their melting point and polymorphic behaviour which were used to produce microspheres using a pilot-scale prilling equipment. The experimental results were compared to theoretical calculations, especially the droplet solidification time which is a key-parameter for this process. This work highlighted that monotropic polymorphism of excipients and supercooling effect have a significant impact on process parameters which should be considered with care during formulation design.

Critical parameters involved in producing microspheres by prilling of molten lipids: from theoretical prediction of particle size to practice.

The aim of this work was to identify the key parameters which influence the running of the prilling process with lipid material from the initial melting to the formation of solid microspheres. The microsphere size would essentially result from break-up at the Rayleigh-Weber's wavelength which mostly depends on the liquid properties (mass density, surface tension and dynamic viscosity). After molten liquid extrusion through the nozzle, the cooling rate is very fast and the instantaneous temperature of the liquid jet decreases rapidly of 0.2-0.3 °C during the duration of the droplet formation (1-2 ms). This leads to no significant modification of the physical characteristics of the lipids and only a very slight change in the dynamic viscosity. Consequently, no significant effect on the optimal wavelength λ(W) and on droplet formation can occur. However, coalescence of liquid droplets has been observed during their fall, probably caused by turbulence into the air column, leading to a minor population of larger microspheres.