Effect of Drug Particle Size on Complexation, Physicochemical Properties and Dissolution of Cyclodextrin Inclusion Complexes

Abstract

The main purpose of this study was to investigate the role of drug particle size on the complexation, physicochemical properties and dissolution of β-cyclodextrin inclusion complexes. In this work, ibuprofen in size of 3 μm and 45 μm (ibuprofen 3 and ibuprofen 45) were employed as the poorly water-soluble drug model. Complexation kinetics and complexation efficiency studies were conducted to investigate the complexation of ibuprofen with β-cyclodextrin in water. The solid cyclodextrins inclusion complexes were prepared with kneading method and characterized by Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray powder difractometry, optical microscopy analyses and dissolution test. Ibuprofen with smaller particle size showed higher complexation rate with β-cyclodextrin in complexation kinetics study. By comparing the apparent stability constant, Kc and complexation efficiency of complexes, it also indicated that smaller drug particles are more efficient to interact with β-cyclodextrin than larger particles. The phase solubility diagram could be classified as Bs type, which denotes complexes with limited solubility. The Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray powder difractometry and optical microscopy analyses confirmed the formation of β-cyclodextrin inclusion complexes with ibuprofen 3 or ibuprofen 45. In the dissolution study, the inclusion complexes presented faster dissolution rate on contrast with the physical mixtures and pure drugs. What is more, the inclusion complexes prepared with ibuprofen in small particle size showed improving dissolution rate than in large particle size.