INFLUENCE OF HYDROXYPROPYL-BETA-CYCLODEXTRIN AND DIMETHYL-BETA-CYCLODEXTRIN ON DIPHENHYDRAMINE INTESTINAL-ABSORPTION IN A RAT IN-SITU MODEL

The influence of complexation of diphenhydramine (DPHA) with hydroxypr opyl-beta-cyclodextrin (HP beta CD) and dimethyl-beta-cyclodextrin (DM beta CD) on intestinal absorption of DPHA has been investigated on an in situ model in rats. The mean apparent stability constants of the c omplexes formed at 23 degrees C between DPHA and the cyclodextrins DM beta CD and HP beta CD were 4988 and 1635 M-1, respectively. At 37 deg rees C, the apparent stability constants were smaller: 895 and 494 M-1 for the complexes formed between DPHA and the cyclodextrins DM beta C D and HP beta CD, respectively. Complexation of DPHA with DM beta CD l ed to a significant decrease (-36%) in the percentage of DPHA absorbed (30.6 +/- 12.0 vs. 22.5 +/- 6.9%, P = 0.018). On the other hand, comp lexation of DPHA with HP beta CD only slightly decreased (-8%) the ext ent of absorption (43.2 +/- 9.0 vs. 40.0 +/- 7.7%, P = 0.16). These da ta suggest that the magnitude of the apparent stability constant of dr ug-cyclodextrin complexes should be considered when complexes are used to increase the oral absorption of drugs. (C) 1998 Elsevier Science B .V. All rights reserved.