Suitability of polymer materials for production of pulmonary microparticles using a PGSS supercritical fluid technique: Thermodynamic behaviour of fatty acids, PEGs and PEG-fatty acids

The thermodynamic behaviour of selected polymeric components for preparation of controlled release microparticles using supercritical carbon dioxide (scCO2) processing was investigated. The polymeric materials selected were egg lecithin (a model for the lung surfactant phospholipid), poly(ethyleneglycol) (PEG) of different molecular weights, fatty acids (C18, C16, and C14), and physical blends of PEGs and fatty acids. In addition a range of PEG-stearates was also assessed. Analysis of thermodynamic behaviour was performed by differential scanning calorimetry (DSC) and by assessment of their interaction with scCO2 in a high-pressure variable volume view cell. The key criterion was to demonstrate a strong interaction with scCO2 and to show liquefaction of the polymeric material at acceptable processing temperatures and pressures. Positive results should then indicate the suitability of these materials for processing by the Particle from Gas Saturated Solutions (PGSS) technique using scCO2 to create microparticles for pulmonary administration. It was found that the materials tested interacted with scCO2 and showed a sufficient lowering of their melting temperature (Tm) to make them suitable for use in the PGSS microparticle production rig. Fatty acids of low Tm were shown to act as a plasticising agent and to lower the Tm of PEG further during interaction with scCO2.

View cell showing PEG 1000 (Tm ∼ 37.5 °C) and palmitic acid (Tm ∼ 62.6 °C) under scCO2 at 35 °C and 140 bar. PEG 1000 has liquefied (Tm depression) and shows flakes of solid palmitic acid dispersed within it.192