COMPARATIVE-STUDY ON INCLUSION-COMPOUNDS OF 4-BIPHENYLACETIC ACID WITH BETA-CYCLODEXTRIN, HYDROXYPROPYLATED-BETA-CYCLODEXTRINS, AND METHYLATED-BETA-CYCLODEXTRINS

The inclusion behavior of Hydroxypropyl-beta-Cyclodextrin (HP-beta-Cyd ) and of methylated-beta-Cyclodextrins, heptakis-(2,6-di-O-methyl)-bet a-Cyclodextrin (DM-beta-Cyd) and heptakis-(2,3,6-tri-O-methyl)beta-Cyc lodextrin (TM-beta-Cyd), in solution and solid state was compared with that of natural beta-Cyclodextrin (beta-Cyd) using an anti-inflammato ry drug, 4-biphenylacetic acid (BPAA), as a guest molecule. The solubi lity of BPAA with beta-Cyd and beta-Cyd derivatives in aqueous solutio n were determined. Stability constants were calculated by phase solubi lity method at various pH values and temperatures. The formation of in clusion complexes with beta-Cyd and beta-Cyd derivatives in the solid state were confirmed by infrared spectroscopy, differential scanning c alorimetry and X-Ray diffractometry, and in the liquid phase by ultrav iolet spectroscopy, circular dichroism and NMR studies. Dissolution ra te and ''in vitro'' release of BPAA from complexes were examined. The results obtained suggest that DM-beta-Cyd is more effective than other beta-Cyclodextrins in improving the pharmaceutical properties of BPAA .