Fluctuation in therapeutic control associated with interchange of prednisolone tablet formulations: assessment of bioequivalence by dissolution test.

Abstract

A 47-year-old woman received combination therapy with prednisolone (PSL), danazol, cepharanthin, ascorbic acid, and cimetidine for the treatment of idiopathic thrombocytopenic purpura. The platelet count was well controlled for over 1 year. Then the PSL tablet formulation was altered from Tablet A to Tablet B with the same treatment regimen, but the platelet counts fell drastically thereafter. However, the platelet counts recovered by changing the PSL tablet formulation back from Tablet B to Tablet A. In vitro dissolution testing was undertaken to assess bioequivalence between Tablet A and Tablet B. PSL in Tablet B was released more slowly compared with that in Tablet A regardless of the medium pH conditions, and the difference in the release rate between the two tablet formulations increased with increasing medium pH value. The difference exceeded the allowance limit (15%) for judgment of bioequivalence under conditions above pH 4, indicating that Tablet A and Tablet B might be nonbioequivalent. The intragastric pH of the patient was probably raised due to coadministration of cimetidine. Therefore the present results suggest that the disparity in the immunosuppressive effects between the two PSL tablet formulations was attributable to the difference in their dissolution behavior in the gastrointestinal tract. We consider that it is better to avoid interchanging PSL tablet formulations in clinical practice.