Cyclodextrins and drug permeability through semi-permeable cellophane membranes

Determinations of drug fluxes through semi-permeable cellophane membranes are used to evaluate cyclodextrin complexes and cyclodextrin containing drug formulations. In the present study we investigated how the cyclodextrin concentration, the membrane thickness and the molecular weight cut off (MWCO) of the membrane influence drug fluxes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and the sample drug was hydrocortisone. The MWCO of the membranes ranged from 500 to 14,000 and the HPbetaCD concentration ranged from 0 to 25% (w/v). The hydrocortisone flux from saturated solutions through the MWCO 500 membrane was unaffected by the cyclodextrin concentration. When MWCO of the membrane was greater than the molecular weight of the complex the flux from solutions saturated with hydrocortisone increased with increasing HPbetaCD concentration. This increase showed negative deviation from linearity. When the flux was corrected for the viscosity increase with increasing HPbetaCD concentration then the flux pattern could be described on the basis of Fick's first law and Stokes-Einstein equation. However. the flux did not correlate with the viscosity when it was increased by adding polymer to the saturated drug solutions. It was shown that the observed flux pattern was consistent with self-association of cyclodextrin complexes in the aqueous donor phase. (C) 2002 Elsevier Science B.V. All rights reserved.