Effects of Generic Prednisolone Formulations on the Dissolution Behavior of Mycophenolate Mofetil under Various pH...

Mycophenolate mofetil (MMF) is a key immunosuppressive agent used after kidney transplantation and is routinely administered in combination with prednisolone (PDN) and tacrolimus (TAC). Although generic MMF products are approved based on bioequivalence, occasional variability in MMF exposure has been reported in clinical practice, raising concerns about formulation-dependent interactions. Because multiple generic PDN formulations containing different pharmaceutical excipients are available, their influence on MMF dissolution warrants regulatory and clinical evaluation. In this study, we investigated the effects of generic PDN formulations on the dissolution behavior of MMF under various pH conditions. In vitro dissolution tests were conducted in accordance with the Japanese Pharmacopoeia using brand-name and generic MMF capsules, administered alone or in combination with originator or generic PDN tablets and TAC. Dissolution profiles were assessed in media at pH 1.2, 4.0, 5.5, and 6.8. MMF and its active metabolite, mycophenolic acid (MPA), were quantified by HPLC, and dissolution ratios were calculated based on the combined dissolved amounts of MMF and MPA. MMF exhibited rapid and nearly complete dissolution at pH 1.2 and pH 4.0 regardless of concomitant administration. At pH 5.5 and pH 6.8, dissolution was reduced, reflecting the intrinsic pH-dependent solubility of MMF. Although minor variations in dissolution profiles were observed in some combination experiments, no reproducible or formulation-dependent differences were identified among PDN products, including generics, and dissolution ratios were comparable across conditions. These findings indicate that generic PDN formulations do not exert a clinically meaningful effect on MMF dissolution under standard conditions, providing regulatory reassurance regarding generic substitution in combination immunosuppressive therapy.