Attachment 1

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. The USP dissolution test for prednisone tablets requires that when 12 tablets are tested, an average of >80% of the labeled amount of prednisone must dissolve in 30 min. The tablets are individually tested under experimental conditions which must be carefully controlled if reproducible results are to be obtained. Four common sources of error associated with Apparatus 2 have been identified: misalignment of equipment, non-uniformity of the bottom curvature of vessels, excess gases in the dissolution medium, and the interaction of the test with slowly disintegrating tablets. Equipment, tools, and technique were developed and improved between 1978 and 1980 to control the first three sources of error. Certain products consist of slowly disintegrating tablets that do not always settle at the center of the bottom of the vessels; such variability of tablet position before disintegration can give imprecise results. However, rapidly disintegrating tablets gave results of sufficient precision to warrant a collaborative study. The purpose of this collaborative study, conducted by 11 laboratories in the second half of 1980, was to measure the reproducibility and repeatability of Apparatus 2 under state-of-theart conditions for prednisone tablets that disintegrate within 5 min. The secondary objectives were to determine whether personnel in many laboratories could correctly adjust Apparatus 2 by following a set of detailed instructions and whether the apparatus would hold the adjustment over an ≈ 2-week test period. E x p e r i m e n t a l Dissolution Test The instructions to collaborators conformed to the USP conditions for testing prednisone tablets with two exceptions. The collaborators were instructed to drop a tablet down the side of the vessel with the paddle rotating rather than to drop a tablet into the vessel and then start paddle rotation. The collaborators were instructed to position each vessel so that its vertical axis was not more than 1 mm at any point from the axis of the paddle shaft. A 2-mm tolerance is allowed in the USP specifications. If this second requirement could not be met, the dissolution drive was deemed unsuitable for the study. All laboratories used similar six-spindle 1 "The United States Pharmacopeia," 20th rev., U.S. Pharmacopeial Convention, Inc., Rockville, Md., 1980, p. 655. 2 D. C. Cox and W. B. Furman, J. Pharm. Sci., 71, 451 (1982). 3 D. C. Cox, C. E. Wells, W. B. Furman, T. S. Savage, and A. C. King, J. Pharm. Sci., 71, 395 (1982). 4 D. C. Cox, W. B. Furman, L. K. Thornton, T. W. Moore, and E. F. Jefferson, J. Pharm. Sci., 72, 910 (1983)