Elemental Impurities in Drug Products

• Autor(a) principal: Brovchenko, Iryna
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/89661
• topic: Elemental impurities; risk assessment; FMEA; ICH; Q3D; ICP-AES; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Elemental Impurities are traces of metals found in medicines, originating from different sources in the product life cycle. ICH has developed the Q3D guideline for 24 Elemental Impurities, divided into 3 classes, based on toxicity and occurrence. Currently, this guideline limits these elements to oral, inhalation and parenteral routes of administration and does not cover the topical route. Initially, it was intended to establish the permitted daily exposure to the topical route, for risk analysis to various pharmaceutical products in order to find those that appeared to be at higher risk for later analysis in the ICP-AES. The risk from the primary packaging material, with subsequent laboratory testing, and a utility (purified water) was also assessed. One of the samples for the analysis was submitted to the digestion process and before the analysis the ICP-AES validation was performed. In the risk analyses it was found that the drugs were below the permitted daily exposure, and that there was one same excipient in the composition of several worst-case products. The greatest risk due to uncertainty was found for one oral solution and two semi-solid products. The analytical method was validated for selectivity, accuracy, linearity, precision, limit of detection and quantification for the 24 elements and proved to be adequate. The detection and quantification limits obtained were optimistic, for example, nickel has a detection and quantification limit of 0.00124 ppm and 0.00375 ppm, respectively. With the ICP-AES it was found that the excipient selected has in its composition Elemental Impurities higher than those accepted in European standards which allows us to conclude that this excipient is one of the main sources of Elemental Impurities for the drugs to which it belongs. There was also a risk associated with semisolid product tubes which yielded arsenic (1.20340 ppm), selenium (0.77105 ppm) and tin (1.15530 ppm).