Lot-to-lot variation in dissolution of tolbutamide tablets.

The dissolution characteristics of tolbutamide tablets made by two manufacturers were compared. Six tablets selected from six lots of each manufacturer were subjected to the USP rotating-basket and paddle-stirrer dissolution tests. Samples were drawn after 10, 20, 30, and 45 minutes for the rotating-basket test and after 10, 20, and 30 minutes for the paddle-stirrer test. Drug concentrations of the dissolution samples were measured by ultraviolet spectroscopy or high-pressure liquid chromatography. All lots passed the disintegration, assay, content uniformity, and tablet weight variation tests; however, there was considerable interlot and intralot variation in the dissolution characteristics of the tablets. The range of interlot differences in the average amount of tolbutamide dissolved using the rotating-basket test was 55.6% for one manufacturer's product and less than 1% for the other's. The ranges were 40.5% and 2.4%, respectively, using the paddle-stirrer test. Similar differences for intralot variation between the two manufacturers' products also existed. Constant patient monitoring appears prudent when products with highly variable dissolution characteristics are used. It is recommended that, for a given patient, the chosen brand of tolbutamide not be changed without careful evaluation.