Comparison of dissolution profiles of brand name and generic drugs of mycophenolate mofetil in the presence of concomitant drugs

Generic drugs have become popular because they reduce medical costs. However, switching from a brand name drug to a generic drug of mycophenolate mofetil (MMF) in immunosuppressive therapy after kidney transplantation resulted in an insufficient increase in its blood concentration in some cases. Immunosuppressive therapy after transplantation typically involves a multidrug strategy. Therefore, changes in efficacy due to switching to a generic drug of MMF may be due to its combination with other drugs. Since the first barrier to the absorption of an orally administered formulation is dissolution, the present study examined the effects of prednisolone (PDN) and tacrolimus (TAC), which are used in immunosuppressive therapy, on the dissolution behavior of MMF. A dissolution experiment was performed in the 1st liquid for dissolution testing (pH 1.2), McIlvaine buffer (pH 4.0), and a 2nd liquid for dissolution testing (pH 6.8) under the single condition of the brand name drug and two generic drugs of MMF as well as under combined conditions with PDN and TAC. Although the initial dissolution rate of MMF differed between the brand name and generic drugs, no significant difference was observed in the final dissolution rate. Furthermore, the f2 value, which evaluates the equivalence of dissolution behavior, was within the standard range. In the 2 nd liquid for dissolution testing (pH 6.8), the dissolution rate and ratio slightly decreased under the combined condition with PDN or TAC; however, in comparisons with the single conditions, the f2 value was within the standard range. Therefore, a reduced blood concentration due to switching to a generic drug of MMF may not be due to a change in dissolution behavior.