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

Abstract

The influence of complexation of diphenhydramine (DPHA) with hydroxypropyl- β-cyclodextrin (HP βCD) and dimethyl- β-cyclodextrin (DM βCD) 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°C between DPHA and the cyclodextrins DM βCD and HP βCD were 4988 and 1635 M −1, respectively. At 37°C, the apparent stability constants were smaller: 895 and 494 M −1 for the complexes formed between DPHA and the cyclodextrins DM βCD and HP βCD, respectively. Complexation of DPHA with DM βCD 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 βCD 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.