Design, production and optimization of solid lipid microparticles (SLM) by a coaxial microfluidic device.

This paper describes a method for the production of lipid microparticles (SLM) based on microfluidics using a newly designed modular device constituted of three main parts: a temperature control, a co-flow dripping element and a congealing element. The presented data demonstrated that the microfluidic approach resulted in the production of SLM with narrow size distribution and optimal morphological characteristics in term of sphericity, surface smoothness and absence of defects (i.e. partial coalescence or irregular shape). The optimization of SLM production was performed by screening the effect of different experimental parameters and device configurations by a classical intuitive approach COST (Changing One Separate factor a Time). This process allowed selecting the proper value for a number of parameters including, (i) the congealing element geometry, (ii) the presence and concentration of a stabilizer, (iii) the temperature of water and oil phases and (iv) the water and oil flow rates. In addition, the interplay between oil phase and water phase flow rates, in controlling the size and morphology of SLM, was investigated by a statistical "Design of the Experiments" approach (DoE). The combined use of COST and DoE studies allowed the production of optimized SLM for the encapsulation of dye/drugs. The obtained results demonstrated that the guest molecules did not affect the general characteristics of SLM, confirming the robustness of the microfluidic procedure in view of the production of SLM for biopharmaceutical and biotech protocols.