This study evaluated the association of N-hexyl-2-methyl-4-nitroimidazol, a model drug, to aggregates formed by anionic polyelectrolytes on aqueous solution. The alternating copolymers of maleic anhydride and N-vinyl-2-pyrrolidone were synthesized and then modified by reaction of the anhydride groups with aliphatic amines and alcohols of varying length of the alkyl chain. The partition of the model drug between water and the hydrophobic microdomains provided by the copolymers was studied using the pseudo-phase model to determinate the distribution coefficient KS, and the standard free energy of transfer ∆µ°t. The results indicate that all copolymers assessed are potential pharmaceutical reservoirs of the model drug. Nevertheless, the solubility of N-hexyl-2-methyl-4-nitroimidazol on the polymeric solutions is independent from the length of the alkyl chain of the copolymer
The effect of amphiphilic polyanion Poly(maleic acid-altoctadecene)sodium salt on solubility of a zwitterionic drug (ampicillin trihydrate) in aqueous media was evaluated. This polymeric salt was obtained by an equimolar reaction of parent copolymer poly Poly(maleic acid-altoctadecene)with an aqueous solution of NaOH. The obtained amphiphilic polyanion was purified by dialysis and lyophilization and was characterized by FTIR spectroscopy. Secondly, a method for the model drug quantification by UV spectrophotometry at 37°C was standardized. Also the grade of association drug-polymer in aqueous media using ultrafiltration methodology at three levels of temperature (20, 30 and 40°C) and two levels of pH (1.2 and 7.4) was determined. Finally, the variation of aqueous solubility of ampicillin trihydrate in ultra-pure water and two buffer media with pH of 1.2 and 7.4 with an ionic strength of 0.15 M at 37°C in presence and absence of amphiphilic polyanion was evaluated. It was found that maximum solubility is reached at a pH value of 1.2 in absence of polymeric material with a value of 36 mg/mL, which diminishes dramatically to a value of 8.3mg/mL when the polyanion is added. In the other side, when the system has a pH value of 7.4, the drug solubility slightly increases from 13 to 16mg/mL in presence of polymeric material, describing that solubility of this kind of drugs is strongly influenced by aqueous media and this type of polymeric materials.
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