Preparation of Drug Nanoparticles by Co-grinding with Cyclodextrin: Formation Mechanism and Factors Affecting Nanoparticle Formation

Abstract

The aim of this study was to investigate the factors affecting the formation of pranlukast nanoparticle prepared by co-grinding with beta-cyclodextrin (beta-CD) and to elucidate the mechanism of nanoparticle formation. The effects of grinding time, moisture content and CD content on the nanoparticle formation were evaluated by means of UV quantitative determination and particle size analysis. High-resolution scanning electron microscopy (HRSEM) was employed to observe drug nanoparticles in the ground mixture. Nanoparticle recovery was higher than 95% for 2 : 1 molecular mixtures of beta-CD : pranlukast which had been ground for 10 min with moisture levels between 10 and 15%. While that of the 1 : 2 ground mixture prepared at 8% moisture level was only 57%. Nanoparticle recovery from beta-CD : pranlukast 2 : 1 mixture ground for 1 min was 2.5%, while that of the 10 min ground mixture was as high as 95%. HRSEM demonstrated that primary drug nanoparticles having a particle size around 50 nm were observed in the ground mixture. The grinding time, the moisture content, and the CD content had significant influences on the formation of drug nanoparticles. The CD matrix may form and stabilize primary particles by its interaction with the particle surface through water molecules. Primary nanoparticles existed in the ground mixture as 50 nm drug nanocrystallites.