Dissolution of Suppositories III: Effect of Insoluble Polyvinylpyrrolidone on Acetaminophen Release

Abstract

Previously reported studies from this laboratory have demonstrated the usefulness of a new apparatus for suppository dissolution study. Acetaminophen suppositories gave slow release and it was posited that addition of a disintegrating agent commonly used in tablet manufacture would increase this release rate. To test the hypothesis, four PEG blends were used as bases as in the previous studies. Each contained 320 mg acetaminophen and 1%, 5%, or 10% of insoluble polyvinylpyrrolidone (Polyplasdone XL^R). One thousand milliliters of phosphate buffer, pH 8.0 to approximate rectal pH was employed as the dissolution media and maintained at 37.5°. A constant agitation rate of 2 5 and 50 rpm was used. Acetaminophen was assayed spectrophotometrically at 243 nm. Comparative dissolution profiles at the various agitation rates and with the concentrations of polyvinylpyrrolidone were developed. Addition of insoluble polyvinylpyrrolidone increased the dissolution rate constant and dissolution half-times at the two agitation rates. While the disintegration aid increased release, this release was not linear with respect to disintegrating agent concentration.

Release of acetaminophen from suppositories and the bioavailability of acetaminophen Erom suppository bases have not received much study. Feldman reported that the rate of bioavailability of suppositories was extremely variable and might not produce a clinically noted response (1). Maron and Ickes, however, reported that acetaminophen suppositories were clinically as effective an antipyretic as were tablets (2).

Pagay, et al. studied the influence of the vehicle on the bioavailability of acetaminophen suppositories using a modified beaker method with a media of pH 7.0 and an agitation of 25 rpm (3). These researchers correlated the dielectric constant of the base to acetaminophen bioavailability. Commercial suppositories were not discussed.

A recent report by Palmieri (4) discussed release of acetaminophen from laboratory prepared PEG bases and commercially available suppositories. Dissolution half-times for laboratory prepared suppositories at 50 rpm ranged from 8 minutes for Base A to 22 minutes for Base D. The commercially available acetaminophen suppositories had a dissolution half-time of 90 minutes at 50 rpm. Because of these apparently slow release rates, it was posited that addition of a disintegrating agent would increase the release of acetaminophen from the polyethylene glycol base sup-positores. Polyplasdone XLR, (5) a crosslinked insoluble homopolymer of n-vinyl-2-pyrrolidone was used in an attempt to increase the release rate.