Design of experiments applied to stress testing of pharmaceutical products: A case study of Albendazole
| Autor: | Moacir Rossi Forim, Regina V. Oliveira, Josiane de Oliveira Cardoso, Luis Guillermo Cuadrado Durango, Bruno Perlatti, Benedito Roberto de Alvarenga Junior, Frederico L.F. Soares, Renato Lajarim Carneiro, Jorge Armando Ardila |
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| Rok vydání: | 2021 |
| Předmět: |
Active ingredient
Anthelmintics Chromatography Central composite design Chemistry Design of experiments Drug Compounding Pharmaceutical Science Hydrogen Peroxide Albendazole Albendazole sulfone Hydrolysis Pharmaceutical Preparations Forced degradation medicine Degradation (geology) medicine.drug Chromatography Liquid |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 165 |
| ISSN: | 1879-0720 |
| Popis: | Forced degradation tests are studies used to assess the stability of active pharmaceutical ingredients (APIs) and their formulations. These tests are performed submitting the API under extreme conditions in order to know the main degradation products in a short period of time. The results of these studies are used to assess the degradation susceptibility of APIs and to validate chromatographic analytical methods. However, most of degradation studies are performed using one-factor-at-the-time (OFAT) which does not consider the interactions between degradation variables. This work proposes the use of Design of Experiment (DoE) approach in forced degradation of albendazole (ABZ). It was used a central composite design (CCD) to evaluate the forced degradation in a multivariate way. Experiments were performed taking into account the variables pH, temperature, oxidizing agent (H2O2) and UV radiation. It was verified the influence of the variables and their interactions on the ABZ degradation. The ABZ oxidation showed to be the main degradation route for ABZ, which is strongly influenced by the temperature. The hydrolysis was relevant at alkaline medium and high temperature. LC-IT-MSn was used to identify the degradation products. It was found three known degradation products (albendazole-2-amino, albendazole sulfoxide and albendazole sulfone) and a new derivate of albendazole molecule (albendazole sulfoxide with a chlorine). This last one was isolated and characterized by UPLC-QToF-MS and NMR analyses. |
| Databáze: | OpenAIRE |
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