Preparation and characterization of quercetin-loaded solid lipid microparticles for pulmonary delivery

Abstract

The aim of this study was to develop quercetin-loaded solid lipid microparticles intended to be inhaled. The microparticles were prepared from a mixture of glyceryl trimyristate and soy lecithin (MGTL), by the hot solvent diffusion method, or from glyceryl behenate, in the presence (MGBL) or absence of soy lecithin (MB), by the hot homogenization method. Quercetin was added to the formulations in a ratio of 1:25 or 1:50 (w/w), regarding the total lipid weight. Particles displaying spherical shape and rough surface were obtained as it was visualized by scanning electron microscopy. The microparticles displayed porosity values varying from 68.83% to 85.94%, low bulk and tapped densities, and good to favorable to tolerable flowability, according to Carr's index. Microparticles prepared from glyceryl trimyristate exhibited acceptable mass aerodynamic diameter (MMAD) for pulmonary administration. However, those prepared from glyceryl behenate and soy lecithin displayed only MMAD50% acceptable values, indicating that barely a powder fraction is able to reach the deeper lung regions. The analyses of the lipid based microparticles and the raw materials evidenced the presence of the β and β′ polymorphs for glyceryl trimyristate and glyceryl behenate, respectively, indicating that no polymorphic transition occurred by using both microparticle preparation techniques. In vitro release studies demonstrated that quercetin release rate is affected for both formulation composition and particle size. The regional deposition of inhaled particles was evaluated using a multi-path model of particle deposition (MPPD). The results indicated that MGTL would be predominantly deposited in the tracheobronchial and pulmonary regions, but a significant fraction of MGBL also may reach the deeper regions of the lung.