دورية أكاديمية
أعرض في EDS

Investigating the root cause of N-nitrosodimethylamine formation in metformin pharmaceutical products.

التفاصيل البيبلوغرافية
العنوان: Investigating the root cause of N-nitrosodimethylamine formation in metformin pharmaceutical products.
المؤلفون: Nasr NEH; Research and Development Department, Al Esraa Pharmaceutical Optima, Badr City, Cairo, Egypt., Metwaly MG; Research and Development Department, Al Esraa Pharmaceutical Optima, Badr City, Cairo, Egypt., Ahmed EO; Research and Development Department, Al Esraa Pharmaceutical Optima, Badr City, Cairo, Egypt., Fares AR; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt., ElMeshad AN; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.; Faculty of Nanotechnology for Postgraduate Studies, Cairo University, El-Sheikh Zayed, Giza, Egypt.
المصدر: Expert opinion on drug safety [Expert Opin Drug Saf] 2021 Jul; Vol. 20 (7), pp. 855-862. Date of Electronic Publication: 2021 Apr 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: England NLM ID: 101163027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-764X (Electronic) Linking ISSN: 14740338 NLM ISO Abbreviation: Expert Opin Drug Saf Subsets: MEDLINE
أسماء مطبوعة: Publication: 2015- : Abingdon, Oxford : Taylor & Francis
Original Publication: London : Ashley Publications, c2002-
مواضيع طبية MeSH: Dimethylnitrosamine/*analysis , Excipients/*analysis , Metformin/*analysis, Chemistry, Pharmaceutical/methods ; Delayed-Action Preparations ; Dimethylnitrosamine/chemistry ; Drug Compounding/methods ; Drug Contamination/prevention & control ; Excipients/chemistry ; Hot Temperature ; Humans ; Metformin/chemistry ; Nitrates/analysis ; Nitrates/chemistry ; Nitrites/analysis ; Nitrites/chemistry ; Tablets ; Water/chemistry
مستخلص: Background: FDA limited N-nitrosodimethylamine (NDMA) - a carcinogenic impurity formed during metformin (MET) tablets manufacturing - level to 96 ng/day; a step which led to recall of MET products. This work aims to investigate the root cause of NDMA formation during MET tablets manufacturing.
Research Design and Methods: We focused on three main contributing causes: use of water and heat during intra-granulation, and the nitrite/nitrate quantities in excipients. Thirteen MET tablet formulations (immediate or sustained-release) were manufactured, on batch level. Each batch was manufactured using one excipient and excluding one cause at a time and NDMA level was assayed.
Results: NDMA traces were undetectable in MET tablets manufactured using polyvinyl pyrrolidone or hydroxypropyl cellulose SSL, even when water and/or heat were employed during intra-granulation. Levels of NDMA in MET tablets with hydroxypropyl methyl cellulose (HPMC) E5 or carboxymethyl cellulose sodium 4000 were 67.08 ± 2.3 and 66.21 ± 2.5 ng/day, in the presence of water and/or heat. No impact of employing extra-granular Polyox TM , HPMC E5 or HPMC K15 on NDMA formation, despite the high nitrite and nitrate content in these excipients.
Conclusions: Water, heat, and excipients' nitrite and nitrate levels are the key players, which should collectively exist, to cause NDMA formation during MET tablets manufacturing.
التعليقات: Comment in: Expert Opin Drug Saf. 2022 Feb;21(2):289. (PMID: 34587843)
فهرسة مساهمة: Keywords: Excipients; hydroxypropyl methyl cellulose; metformin HCL; n-nitrosodimethylamine; polyvinyl pyrrolidone; tablets
المشرفين على المادة: 0 (Delayed-Action Preparations)
0 (Excipients)
0 (Nitrates)
0 (Nitrites)
0 (Tablets)
059QF0KO0R (Water)
9100L32L2N (Metformin)
M43H21IO8R (Dimethylnitrosamine)
تواريخ الأحداث: Date Created: 20210414 Date Completed: 20210813 Latest Revision: 20220425
رمز التحديث: 20221213
DOI: 10.1080/14740338.2021.1917547
PMID: 33849366
قاعدة البيانات: MEDLINE
الوصف
تدمد:1744-764X
DOI:10.1080/14740338.2021.1917547