Co-grinding with Cyclodextrin as a Nanoparticle Preparation Method of a Poorly Water Soluble Drug

摘要

The method of co-grinding with cyclodextrins (CDs) was applied to a poorly water soluble drug,ONO-8713 (solubility;0.92 ug/ml in H_2O at 25 deg C) as a method to prepare nanoparticles.ONO-8713 was co-ground with various CDs in a vibration mill.alpha-Cyclodextrin,beta-CD,gamma-CD,CD derivatives and some sugars were used as co-grinding additives.Suitable moisture content in the co-grinding system was required to achieve maximum nanoparticle yield.When ONO-8713 was co-ground with beta-CD (molar ratio of beta-CD:drug = 5:1) at 12% moisture,85% of drug recovered as nanoparticles with a mean particle size of 120 nm.Nanoparticle yield achieved 90% when hydroxypropyl-beta-CD was used as a co-grinding additive.It was found that the amount of drug nanoparticles depended on the characteristics of CDs.This phenomenon was probably due to the difference in the cavity size of CDs along with the variation of substitution groups that affected the interaction between CDs and drug,and the affinity between CD and drug molecules.Zeta potential analysis suggested that CD would form a layer covering on the particle surface and alter the charge of the particles,improving the stability and total yield of the nanoparticle.