In vitro-in vivo correlation in the effect of cyclodextrin on oral absorption of poorly soluble drugs

Int J Pharm. 2021 May 1;600:120494. doi: 10.1016/j.ijpharm.2021.120494. Epub 2021 Mar 17.


In this study the concentration effect of 2-Hydroxypropyl-beta-cyclodextrin (HP-βCyD) on oral drug absorption of the BCS class II drugs Danazol (DNZ) and Albendazole (ABZ) was evaluated. In vitro permeation of solutions and suspension systems was compared with their in vivo intestinal absorption in rats and their in vitro-in vivo correlation assessed. In solutions excess amounts of HP-βCyD decreased both in vitro permeation and in vivo absorption due to the decrease in free drug concentration, as expected. However, in suspension systems the contribution of HP-βCyD by drug complexation was found to be altered by further rate limiting steps for membrane permeation and intestinal absorption of each drug. In vitro permeation of DNZ was rate-limited by the diffusion into the unstirred water layer (UWL), while that of ABZ was rate-limited by the permeation across the lipid membrane. For the in vivo intestinal absorption, both drugs were rate-limited by the dissolution rate from undissolved drug. These differences in the rate-limiting process were considered to cause discrepancies in the result of in vitro and in vivo assays. In conclusion, it is quite important to understand the rate limiting process of oral absorption of the target drug for designing oral liquid formulations containing cyclodextrins.

Keywords: Cyclodextrin; In vitro-in vivo correlation; Solubility-permeability balance; The rate limiting process.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Administration, Oral
  • Animals
  • Cyclodextrins*
  • Intestinal Absorption
  • Permeability
  • Pharmaceutical Preparations*
  • Rats
  • Solubility


  • Cyclodextrins
  • Pharmaceutical Preparations
  • 2-Hydroxypropyl-beta-cyclodextrin