*Article* **Modeling of the Production of Lipid Microparticles Using PGSS**® **Technique**

**Clara <sup>L</sup>ópez-Iglesias 1,\*, Enriqueta R. <sup>L</sup>ópez 2, Josefa Fernández 2, Mariana Landin 1 and Carlos A. García-González 1,\***


Academic Editor: Rita Cortesi

Received: 25 September 2020; Accepted: 23 October 2020; Published: 24 October 2020

**Abstract:** Solid lipid microparticles (SLMPs) are attractive carriers as delivery systems as they are stable, easy to manufacture and can provide controlled release of bioactive agents and increase their efficacy and/or safety. Particles from Gas-Saturated Solutions (PGSS®) technique is a solvent-free technology to produce SLMPs, which involves the use of supercritical CO2 (scCO2) at mild pressures and temperatures for the melting of lipids and atomization into particles. The determination of the key processing variables is crucial in PGSS® technique to obtain reliable and reproducible microparticles, therefore the modelling of SLMPs production process and variables control are of grea<sup>t</sup> interest to obtain quality therapeutic systems. In this work, the melting point depression of a commercial lipid (glyceryl monostearate, GMS) under compressed CO2 was studied using view cell experiments. Based on an unconstrained D-optimal design for three variables (nozzle diameter, temperature and pressure), SLMPs were produced using the PGSS® technique. The yield of production was registered and the particles characterized in terms of particle size distribution. Variable modeling was carried out using artificial neural networks and fuzzy logic integrated into neurofuzzy software. Modeling results highlight the main effect of temperature to tune the mean diameter SLMPs, whereas the pressure-nozzle diameter interaction is the main responsible in the SLMPs size distribution and in the PGSS® production yield.

**Keywords:** lipid microparticles; PGSS®; supercritical CO2; modeling; solvent-free technology
