Influence of hydroxypropyl-β-cyclodextrin and dimethyl-β-cyclodextrin on diphenhydramine intestinal absorption in a rat in situ model

The influence of complexation of diphenhydramine (DPHA) with hydroxypropyl-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 complexes 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 degrees C, the apparent stability constants were smaller: 895 and 494 M-1 for the complexes formed between DPHA and the cyclodextrins DM beta CD and HP beta CD, respectively. Complexation of DPHA with DM beta CD led 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, complexation of DPHA with HP beta CD only slightly decreased (-8%) the extent of absorption (43.2 +/- 9.0 vs. 40.0 +/- 7.7%, P = 0.16). These data suggest that the magnitude of the apparent stability constant of drug-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.