N-nitrosamine Mitigation with Nitrite Scavengers in Oral Pharmaceutical Drug Products.

Antioxidants Drug design Drug-excipient interactions Excipient(s) Inhibition Nitrosamine formation Stability Tablet(s)

Journal

Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R

Informations de publication

Date de publication:
07 2023
Historique:
received: 09 01 2023
revised: 16 03 2023
accepted: 29 03 2023
medline: 19 6 2023
pubmed: 7 4 2023
entrez: 6 4 2023
Statut: ppublish

Résumé

N-nitrosamines are likely human carcinogens. After N-nitrosamine contaminants were detected in pharmaceutical products in 2018, regulatory authorities set a framework for the risk assessment, testing and mitigation of N-nitrosamines in drug products. One strategy to inhibit the formation of N-nitrosamines during the manufacture and storage of drug products involves the incorporation of nitrite scavengers in the formulation. Diverse molecules have been tested in screening studies including the antioxidant vitamins ascorbic acid and α-tocopherol, amino acids, and other antioxidants used in foods or drugs, for inclusion into drug products to mitigate N-nitrosamine formation. This review article outlines key considerations for the inclusion of nitrite scavengers in oral drug product formulations.

Identifiants

pubmed: 37023856
pii: S0022-3549(23)00142-9
doi: 10.1016/j.xphs.2023.03.022
pii:
doi:

Substances chimiques

Nitrosamines 0
Nitrites 0
Antioxidants 0
Ascorbic Acid PQ6CK8PD0R
Pharmaceutical Preparations 0

Types de publication

Journal Article Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1794-1800

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.-C.V.B, Z.M., R.T.S., M.W., M.F. and A.B. are employees of DSM Nutritional Products Ltd., Kaiseraugst, Switzerland. J.K.B is a consultant for and former employee of DSM Nutritional Products Ltd. Kaiseraugst, Switzerland.

Auteurs

Anne-Cécile V Bayne (AV)

DSM Nutritional Products, 6480 Dobbin Road, Columbia, MD, United States of America. Electronic address: Anne-Cecile.Bayne@dsm.com.

Zdravka Misic (Z)

DSM Nutritional Products Ltd., P.O. Box 2676, 4002, Basel, Switzerland.

René T Stemmler (RT)

DSM Nutritional Products Ltd., P.O. Box 2676, 4002, Basel, Switzerland.

Marc Wittner (M)

DSM Nutritional Products Ltd., P.O. Box 2676, 4002, Basel, Switzerland.

Margarita Frerichs (M)

DSM Nutritional Products Ltd., P.O. Box 2676, 4002, Basel, Switzerland.

Julia K Bird (JK)

Bird Scientific Writing, Wassenaar, 2242, the Netherlands.

Ahmed Besheer (A)

DSM Nutritional Products Ltd., P.O. Box 2676, 4002, Basel, Switzerland.

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Classifications MeSH