The effects of cyclodextrins on drug release from fatty suppository bases: I. In vitro observations

The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories were prepared, containing the pure drug, a physical mixture of drug and cyclodextrin and the drug-cyclodextrin complex, respectively. A simple in vitro model was used to study the release characteristics of the different suppositories. The results showed the highest release for the drug-cyclodextrin complexes. The release mechanism of the complexes could be described as follows: the complex, being insoluble in the lipophilic base, is present as a suspension of particles; these particles are transported to the lipid-water interface by sedimentation; due to the hydrophilic character of the cyclodextrins the particles then enter the aqueous layer where they dissolve. The drug release is consequently influenced by the dissolution rate of the complexes. After dissolution the complex will partially dissociate and free drug will be formed. When drugs with a high o/w partition coefficient were used this free drug diffused back into the lipid layer, thereby decreasing the final drug release. For drugs with low stability constants the improvements of drug release obtained by complexation were limited by back diffusion.