Comparison of Dissolution Properties of 2 Enteric-Coated Formulations Containing Mycophenolate Sodium: Myfortic vs Femulan

• Published in: Transplantation proceedings 2010, Vol.42 (1), p.353-356
• Main Authors: Esquivel, A, González-Ramírez, R, Alberú, J, Gracida, C, Medeiros, M, Castañeda-Hernández, G
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Stability; Drugs, Generic - chemistry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hydrogen-Ion Concentration; Immunosuppressive Agents - chemistry; Medical sciences; Mexico; Mycophenolic Acid - chemistry; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Pharmacology. Drug treatments; Sodium; Solubility; Solutions; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tablets, Enteric-Coated; Tissue, organ and graft immunology
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.11.015

Abstract Enteric-coated tablets containing mycophenolate sodium have been developed to reduce gastric toxicity. The objective of this study was to compare 2 enteric-coated formulations containing 360 mg of mycophenolate sodium: the innovator product, Myfortic, and an agent that recently became available in Mexico, Femulan. For both formulations, mycophenolate sodium content was within the 90% to 110% range of the label claimed dose, and no impurities were present as determined at high-performance liquid chromatography. Mycophenolate sodium release was assayed by applying the US Pharmacopeia apparatus 2 dissolution test at 2 different pH values (1.2 and 6.8) to mimic conditions in the stomach and the small intestine, respectively. At pH 1.2, mycophenolate sodium release was less than 2%, with respect to the label claimed dose, for both formulations. At pH 6.8, mean (range) mycophenolate sodium release with Myfortic was 104.9% (104.0%–105.6%), and with femulan was 62.3% (51.3%–67.7%); the difference between formulations achieved statistical significance ( P = .04). Moreover, intratablet variability with the generic formulation was unacceptable. Variation between the highest and lowest drug release was 32.0% for Femulan, and 1.02% for Myfortic. Thus, it is likely that Femulan results in insufficient and irreproducible absorption of mycophenolate sodium in the small intestine, leading to inadequate immunosuppressive efficacy. It is concluded that Femulan and myfortic are not equivalent formulations. Furthermore, Femulan is not a suitable formulation for clinical use in organ transplantation because it does not meet pharmaceutical quality standards.