Comparative study on Inclusion compounds of 4-Biphenylacetic acid with β-Cyclodextrin, Hydroxypropylated-β-Cyclodextrins, and methylated-β-Cyclodextrins

Abstract

The inclusion behavior of Hydroxypropyl-β-Cyclodextrin (HP-β-Cyd) and of methylated-β-Cyclodextrins, heptakis-(2,6-di-O-methyl)-β-Cyclodextrin (DM-β-Cyd) and heptakis-(2,3,6-tri-O-methyl)-β-Cyclodextrin (TM-β-Cyd), in solution and solid state was compared with that of natural β-Cyclodextrin (β-Cyd) using an anti-inflammatory drug, 4-biphenylacetic acid (BPAA), as a guest molecule. The solubility of BPAA with β-Cyd and β-Cyd derivatives in aqueous solution were determined. Stability constants were calculated by phase solubility method at various pH values and temperatures. The formation of inclusion complexes with β-Cyd and β-Cyd derivatives in the solid slate were confirmed by infrared spectroscopy, differential scanning calorimetry and X-Ray diffractometry, and in the liquid phase by ultraviolet spectroscopy, circular dichroism and NMR studies. Dissolution rate and “in vitro” release of BPAA from complexes were examined. The results obtained suggest that DM-β-Cyd is more effective than other β-Cyclodextrins in improving the pharmaceutical properties of BPAA.