Interaction of anionic compounds with gelatin. I: Binding studies.

Even though gelatin is the most widely used polymeric excipient in pharmaceutical products, scant attention has been paid to its interaction with small organic molecules. The present work deals with the interaction of gelatin and four monosulfonated or monocarboxylated azo dyes having hydrocarbon moieties of different sizes. These dyes were used as models for anionic drugs, which make up a significant percentage of all new drugs. Most binding studies used ultrafiltration to separate free from bound dye, followed by spectrophotometric dye assays. One binding study was based on the shift in pH when a dye was added to gelatin solutions. All binding isotherms consisted of two linear segments. The initial segments, which start at the origin, represent the partitioning of the dyes between the dissolved gelatin and the aqueous buffer solution. They changed abruptly to horizontal plateaus, which represent the binding limit. Increases in pH from 5.00 to 7.00 reduced the binding of the sulfonated dyes but increased the binding of the carboxylated dye. At pH > or = 7.00, where even the carboxylic acid groups are fully ionized, the carboxylated dye and its sulfonated analog were bound to gelatin to the same extent. The binding of all dyes decreased with increasing temperature (i.e., the standard enthalpy of binding was negative), with a change of the solvent medium from water to 0.15 M ammonium acetate, and with decreasing size of the hydrocarbon moieties of the dyes. The binding of the dyes to gelatin was always reversible and the standard entropy change associated with it was negative.(ABSTRACT TRUNCATED AT 250 WORDS)