HYDROPHOBICALLY MODIFIED POLYELECTROLYTES AS POTENTIAL DRUGS RESERVOIRS OF N-ALKYL-NITROIMIDAZOLES

The solubilization of three commercial drugs (omindazole, metronidazole and tinidazole) and model compounds (N-alkyl-2-methyl-4-nitroitnidazoles) on aggregates formed by anionic polyelectrolytes, carrying alkyl side chains of different length, have been investigated in aqueous solution at PH 3.0, 7.0 and 11.0. Potassium salts of poly(maleic acid-co-1-olefins), PA-nK(2) with n ranging from 8 to 18, were used as micelle-forming polymers. The partition of these drugs between water and the hydrophobic microdomains provided by PA-nK2 was studied by the pseudo-phase model to determinate the distribution coefficient K-s, and the standard free energy of transfer Delta mu(o)(t). The results indicate that solubility of alkyl-nitroimidazoles on these polynner micelles depends moderately on the length of the alkyl chain, and therefore is mainly determined by the heterocyclic group. On the other hand, the solubilization of 1-hexyl-2-methyl-4-nitroimidazole increase with decreasing length of the side alkyl chain; i.e. K-s follows the order PA-8K(2) > PA-10K (2) > PA-12K(2) > PA-14K(2), > PA-16K(2,) > PA-18K(2).