How interactions between drugs and agarose-carrageenan hydrogels influence the simultaneous transport of drugs.

The diffusional transport of a series of small drug molecules (<400 Da) in agarose gel with and without kappa-carrageenan (a negatively charged polysaccharide) is studied. The drug molecules have amphiphile character, the hydrophilic part being a tertiary amine which is the same in all six drugs. The difference in structure resides in the hydrophobic part which give these molecules different properties such as a difference in CMC-values (critical micelle concentration). The transport studies show that the apparent diffusion coefficients (Dapp) of all the drugs in 1% (w/w) agarose gel are almost identical and with a value similar to that in water. These results were anticipated because of the small size of the drugs, the low concentration of agarose, and the lack of interaction between the diffusant and the polymer. In agarose gels also containing 0.02% (w/w) kappa-carrageenan, however, the Dapp-values are significantly decreased for all drugs, except for lidocaine. This lowering of the Dapp is ascribed to the interaction between the drug molecules and kappa-carrageenan. The Dapp-values of the drugs in the gel system containing kappa-carrageenan correlate well with the adsorption isotherms of the same drugs in the drug/kappa-carrageenan/water system obtained previously [1] and the Dapp-values follow the order: chlorpromazine<clomipramine<amitriptyline<imipramine<doxepin. Chlorpromazine has the lowest Dapp, with the highest degree of adsorption, and doxepin with the lowest degree of adsorption has the highest Dapp. Furthermore, results from the simultaneous transport of two drugs, chlorpromazine and amitriptyline, in the agarose gel containing kappa-carrageenan are also presented and clearly indicate a transport competition with good correlation to the adsorption isotherms.