Suitability of polymer materials for production of pulmonary microparticles using a PGSS supercritical fluid technique: preparation of microparticles using PEG, fatty acids and physical or chemicals blends of PEG and fatty acids

Abstract

The production of microparticles using a supercritical carbon dioxide based PGSS technique (CriticalMix™) has been exploited to develop blended systems targeted at pulmonary delivery. Hence, PEG based polymers of different molecular weights (1000-6000 Da) were blended in situ with fatty acids (stearic, palmitic or myristic acid) or with commercially available PEG-stearates. The effect of the different thermodynamic properties of the polymers was evaluated by characterising the microparticles produced in terms of their melting temperature by conventional DSC and in the presence of high pressure CO(2) using a high pressure variable volume view cell. The microparticles produced were also assessed by SEM and particle size distribution. It is well known that as the molecular weight of the PEG chains increases, so does the viscosity of the melt and this leads to an increase in the particle size. In the paper we show that blending with myristic acid provides optimal control of particle size when the blend is sprayed from scCO(2) leading to high yields in the optimal aerodynamic size range of 2-5 μm for the deep lung delivery. The highest yield and smallest particles (~5 μm) were produced with a blend of PEG 3000 and myristic acid (1:1) whereas the batches containing palmitic acid and stearic acid showed lower yields and larger particle sizes.