In-use stability assessment of FDA approved metformin immediate release and extended release products for N-Nitrosodimethylamine and dissolution quality attributes

• Published in: International journal of pharmaceutics 2022-07, Vol.623, p.121923-121923, Article 121923
• Main Authors: Dharani, Sathish, Mohamed, Eman M., Khuroo, Tahir, Ali, Hamed I., Reddy, Indra K., Rahman, Ziyaur, Khan, Mansoor A.
• Format: Article
• Language: English
• Subjects: Extended release, in-use stability, dissolution; Immediate release; Metformin; N-nitrosodimethylamine
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.121923

[Display omitted] Metformin is a widely used first-line oral antidiabetic agent. TheFood and Drug Administration (FDA) confirmed the presence of the ofN-nitrosodimethylamine (NDMA) impurity, a carcinogenic, above the acceptable daily intake (ADI, 96 ng/day) in certain metformin products. The objective of the present study was to assess in-use stability of commercial metformin products for NDMA and dissolution quality attributes. Four immediate-release (M1-M4) and six extended-rerelease (M5-M10) metformin products were evaluated in the stability testing. All products were repacked in pharmacy vials and stored at 30 °C/75% RH for 12 weeks. Five products (M2, M3, M5, M7 and M10) had NDMA level above ADI limit (96 ng/day) before in-use stability exposure. NDMA in M2 (1164 ± 52.9 ng/tablet) and M3 (3776 ± 351.9 ng/tablet) products were 12 and 39 folds of ADI, respectively. Similarly, ER products, M5 (191 ± 94.1 ng/tablet), M7 (1473 ± 47.3 ng/tablet) and M10 (423 ± 55.8 ng/tablet) exhibited NDMA of 1.9, 15.3 and 4.4 folds of ADI, respectively. The impurity level significantly (p