Thermal stability kinetics and shelf life estimation of the redox-active therapeutic and mimic of superoxide dismutase enzyme, Mn(III) meso-Tetrakis(N-ethylpyridinium-2-yl)porphyrin Chloride (MnTE-2-PyPCl5, BMX-010)
Carregando...
Data
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Minas Gerais
Descrição
Tipo
Artigo de periódico
Título alternativo
Primeiro orientador
Membros da banca
Resumo
Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride (MnTE-2-PyPCl5, BMX-010, and AEOL10113) is among the most studied superoxide dismutase (SOD) mimics and redox-active therapeutics, being currently tested as a drug candidate in a phase II clinical trial on atopic dermatitis and itch. The thermal stability of active pharmaceutical ingredients (API) is useful for estimating the expiration date and shelf life of pharmaceutical products under various storage and handling conditions. The thermal decomposition and kinetic parameters of MnTE-2-PyPCl5 were determined by thermogravimetry (TG) under nonisothermal and isothermal conditions. The first thermal degradation pathway affecting Mn-porphyrin structural integrity and, thus, activity and bioavailability was associated with loss of ethyl chloride via N-dealkylation reaction. The thermal stability kinetics of the N-dealkylation process leading to MnTE-2-PyPCl5 decomposition was investigated by using isoconversional models and artificial neural network. The new multilayer perceptron (MLP) artificial neural network approach allowed the simultaneous study of ten solid-state kinetic models and showed that MnTE-2-PyPCl5 degradation is better explained by a combination of various mechanisms, with major contributions from the contraction models R1 and R2. The calculated activation energy values from isothermal and nonisothermal data were about 90 kJ mol–1 on average and agreed with one another. According to the R1 modelling of the isothermal decomposition data, the estimated shelf life value for 10% decomposition (t90%) of MnTE-2-PyPCl5 at 25°C was approximately 17 years, which is consistent with the high solid-state stability of the compound. These results represent the first study on the solid-state decomposition kinetics of Mn(III) 2-N-alkylpyridylporphyrins, contributing to the development of this class of redox-active therapeutics and SOD mimics and providing supporting data to protocols on purification, handling, storage, formulation, expiration date, and general use of these compounds.
Abstract
Assunto
Cinética química, Farmacocinética, Termogravimetria, Redes neurais (Computação), Pele - Doenças, Superóxido desmutase, Porfirina e compostos de porfirina
Palavras-chave
Thermal stability kinetics, Thermogravimetry, Diferential thermal analyses, Superoxide dismutase mimics, Redox-active therapeutics
Citação
Departamento
Curso
Endereço externo
https://onlinelibrary.wiley.com/doi/10.1155/2021/7003861
Coleções
Avaliação
Revisão
Suplementado Por
Referenciado Por
Licença Creative Commons
Exceto quando indicado de outra forma, a licença deste item é descrita como Acesso aberto