Alkylamine-carboxymethyl cellulose salts: Preparation, characterization and pharmaceutical applications

摘要

A series of novel mixed alkylamine salts of carboxymethyl-cellulose of varying stoichiometry were prepared and evaluated for their utility as films and bead forming materials. Homologous primary alkylamines from the inclusive set decyl through octadecyl were used at equivalent fractions of 0.1, 0.2, 0.4, 0.6, 0.8 and 1.0. Films of uniform thicknesses in the range 14$mu$m to 20$mu$m were prepared by casting on glass plates. Beads were prepared in the range 1mm to 3mm diameter by dispersion of droplets of polyanion solution in solutions of the amines.;Films were evaluated for moisture absorption, water vapor transmission, solubility, tensile strength and thermal characteristics. Beads were evaluated for solubility as a function of the acidity or basicity of aqueous media in which they were dispersed, rate of formation and extent of alkylamine incorporation. In addition, beads were evaluated for the influence of composition on rate of release of a contained model drug, theophylline, in neutral, acidic and alkaline media.;The moisture absorption, water vapor transmission, mechanical strength and crystallinity of the films were seen to decrease compared to sodium carboxymethylcellulose. These changes were seen when the proportion of amine in the salt-film were increased and also, as the size of the normal alkyl group of the amine increased. The solubility of alkylamine carboxymethylcellulose films varied with the pH value of the dissolution medium, rising to a maximum at about a pH value of eight. Release of the model drug theophylline from bead formulations showed an initial "burst" effect at all pH values. Theophylline release was limited to about twenty percent of total drug at acidic pH values but approached complete release over an extended time period in simulated intestinal fluid.