Systematic error associated with apparatus 2 of the USP dissolution test V: Interaction of two tableted prednisone formulations with glass and plastic vessels.

Recently marketed glass vessels that are uniform and pass USP specifications were compared with uniform plastic vessels that also pass USP specifications. Two lots of prednisone tablets, Tablet 1 and Tablet 2, were tested in both types of vessels. Tablet 1 gave higher results (+12.7% of label claim) in glass vessels at 50 rpm but gave equivalent results in either vessel at 75 rpm. Tablet 2 gave equivalent results in either vessel at 50 rpm but gave higher results (+22% of label claim) in glass vessels at 75 rpm. The type of vessel used to obtain dissolution results for tablets should be specified.

Collaborative study of the USP dissolution test for prednisone tablets with Apparatus 2.

Five lots of prednisone tablets that disintegrate within 5 min were collaboratively studied by 11 laboratories using USP Apparatus 2 under carefully controlled conditions. One lot gave complete dissolution. The reproducibility and repeatability of Apparatus 2 for the four lots still dissolving at the end of the test were 2.6 and 1.6% of label claim, respectively, for the 11 laboratories.

Systematic error associated with apparatus 2 of the USP dissolution test IV: effect of air dissolved in the dissolution medium.

Acceptable concentrations of gases in a medium are not well defined in USP dissolution tests. A sample of 10-mg prednisone tablets, known to be sensitive to dissolved gases, was tested with batches of purified water that contained different concentrations of air. The data suggest that the results from Apparatus 2 can be influenced by the concentration of air in the dissolution medium unless the medium remains unsaturated with air for the duration of the test. The repeatability of means of six results was markedly improved when the air concentration in the medium was accurately controlled at the beginning of the test.

Systematic error associated with apparatus 2 of the USP dissolution test III: limitations of calibrators and the USP suitability test.

The calibrator tablets now used in the USP suitability test do not reveal common sources of systematic error associated with Apparatus 2. When the apparatus was operated under conditions near or beyond USP tolerances, changes in the results of the USP calibrators were slight, whereas those of several samples of commercial prednisone tablets were significant. Thus, the USP calibrators and requirements do not guarantee suitability of the equipment for general dissolution testing of drug products.

Simultaneous assay of thioridazine and its major metabolites in plasma at single dosage levels with a novel report of two ring sulfoxides of thioridazine.

A highly sensitive and selective method of analysis of plasma for thioridazine and its major metabolites, including two isomers of the ring sulfoxide, is presented. It is suitable for following the metabolism of thioridazine for 24 hr after a single dose. The method involves extraction of the materials from plasma, high-performance liquid chromatographic separation, and postcolumn oxidation and fluorometric detection. The sensitivity of the method to thioridazine and its metabolites is 2 ng/ml. Recoveries ranged from 87.8 to 100.6% at levels between 20 and 400 ng/ml.

Systematic error associated with apparatus 2 of the USP dissolution test II: Effects of deviations in vessel curvature from that of a sphere.

Dissolution vessels made from glass or plastic are recognized by the USP as being suitable for dissolution testing. Glass vessels with a bottom inside curvature flatter than that of a sphere can cause a high bias in dissolution results; vessels with a steeper curvature can cause a low bias. The inside bottom curvature of plastic vessels adhered closely to the curvature of a sphere. The plastic vessels are preferable for use if the drug is not adsorbed and the vessel is not attacked by the dissolution medium. Bias in results between individual positions of a dissolution apparatus was traced to two shafts which were not vertical.

Procedure for calibrating the Technicon Colorimeter I.

We describe a rapid method for calibrating the Technicon AutoAnalyzer colorimeter I. Test solutions of bromphenol blue are recommended for the calibration, in preference to solutions of potassium dichromate, based on considerations of the instrument's working range and of the stray light characteristics of the associated filters.