RESUMO
OBJECTIVES: In the present study, Cinnarizine was selected as a weakly basic drug with poor aqueous solubility to investigate the supersaturation maintaining the ability of different types of anionic Eudragit polymers (Eudragits L100-55, L100 and S100). Furthermore, the interplay between polymer-mediated supersaturation maintenance and in vitro permeation enhancement was studied. METHODS: The effect of Eudragit polymers on the pH-induced supersaturation of Cinnarizine was examined under different pHs (6.4, 6.8, and 7.8). Moreover, the effect of Eudragit polymers on the permeation of Cinnarizine through the Caco-2 membrane was investigated. RESULTS: The aggregate size of Eudragit polymers in solution was determined and it was found that the size of polymer aggregate was bigger when lower pH or more hydrophobic polymer was used, which corresponded strongly with improved drug supersaturation. Based on the findings, hydrophobic Cinnarizine-polymer interactions seemed to be essential in determining the impact of Eudragit polymers on maintaining the Cinnarizine supersaturation. The permeation study demonstrated that the rate of drug permeation through the Caco-2 membrane increased in the presence of Eudragit polymers, but their effect on maintaining supersaturation was more significant than their effect on the drug permeation rate. Moreover, the highest level of Cinnarizine supersaturation observed in a non-permeation condition did not correlate with the optimal absorption in a permeation condition. CONCLUSION: This study revealed that the integration of permeation and supersaturation assays is needed to reliably predict the impact of supersaturation maintenance by polymers on the absorption of poorly soluble drugs.
