Abstract
Most drugs permeate biological membranes via passive diffusion and it is generally assumed that the main barrier is the lipophilic structure of the membranes. However, it has been observed that an unstirred water layer adjacent to the membrane surface can in some cases be just as effective barrier as the lipophilic membrane itself. Hydrophilic cyclodextrins can enhance drug delivery through biological membranes by increasing the availability of dissolved drug molecules immediate to the membrane surface, i.e., by increasing drug delivery through the unstirred water layer. We have developed an artificial octanol membrane that is cheap and simple to prepare. The novel membrane consists of a hydrated semi-permeable cellophane membrane with a molecular weight cut off (MWCO) of 12,000–14,000 that mimics the unstirred water layer and a lipophilic membrane of pure n-octanol in a nitrocellulose matrix. The membrane was used to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HPβCD) on the flux of hydrocortisone through the membrane. In aqueous HPβCD saturated with hydrocortisone the drug concentration gradient, over the unstirred water layer, increased with increasing HPβCD concentration which resulted in enhanced drug delivery through the membrane. When excess HPβCD was present in the donor phase the octanol/water partition coefficient decreased with increasing HPβCD concentration that lead to decreased drug delivery through the membrane.
Published Version
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