NERDG 2026
Poster 30 Abstract
Impact of antioxidant addition on drug dissolution: Implications for NDSRI mitigation biowaivers
Rutu R Valapil, James E Polli
University of Maryland Baltimore
Presenting and Corresponding Author: Rutu R Valapil, [email protected]
Abstract
Nitrosamine impurities have garnered recent attention due to their presence in medications and mutagenic properties. FDA guidelines emphasize controlling impurities and suggest ways to mitigate further formation of nitrosamine by addition of antioxidants. However, practical experience with this new guidance update remains limited. This study investigated the impact of added antioxidants on dissolution using diclofenac potassium, belonging to BCS class II as a model drug. Six antioxidants were tested for their effect on in vitro dissolution. Two tablet formulation types with 50mg of Diclofenac potassium were fabricated with and without antioxidants. Tablets were subjected to in vitro dissolution in simulated intestinal fluid(USP SIF) and sodium bicarbonate buffer. Dissolution profiles were compared using similarity factor(f2). Results show the feasibility of added antioxidant to not impact dissolution. When dissolution was impacted, dissolution dissimilarity appeared to be due to coning, as apex vessels substantially eliminated slower dissolution. An unlikely explanation of antioxidant effect was that antioxidant locally decreased pH to cause slower dissolution of the weakly acidic drug.
Keywords
Nitrosamine, Antioxidants, Dissolution, Nitrosamine mitigation
Poster 30 Abstract
Impact of antioxidant addition on drug dissolution: Implications for NDSRI mitigation biowaivers
Rutu R Valapil, James E Polli
University of Maryland Baltimore
Presenting and Corresponding Author: Rutu R Valapil, [email protected]
Abstract
Nitrosamine impurities have garnered recent attention due to their presence in medications and mutagenic properties. FDA guidelines emphasize controlling impurities and suggest ways to mitigate further formation of nitrosamine by addition of antioxidants. However, practical experience with this new guidance update remains limited. This study investigated the impact of added antioxidants on dissolution using diclofenac potassium, belonging to BCS class II as a model drug. Six antioxidants were tested for their effect on in vitro dissolution. Two tablet formulation types with 50mg of Diclofenac potassium were fabricated with and without antioxidants. Tablets were subjected to in vitro dissolution in simulated intestinal fluid(USP SIF) and sodium bicarbonate buffer. Dissolution profiles were compared using similarity factor(f2). Results show the feasibility of added antioxidant to not impact dissolution. When dissolution was impacted, dissolution dissimilarity appeared to be due to coning, as apex vessels substantially eliminated slower dissolution. An unlikely explanation of antioxidant effect was that antioxidant locally decreased pH to cause slower dissolution of the weakly acidic drug.
Keywords
Nitrosamine, Antioxidants, Dissolution, Nitrosamine mitigation
