Design of experiments applied to stress testing of pharmaceutical products: A case study of Albendazole

Author(s)

Ardila, Jorge Armando ^[1] ; de Alvarenga Junior, Benedito Roberto ^[1] ; Durango, Luis Cuadrado ^[1] ; Felipe Soares, Frederico Luis ^[2] ; Perlatti, Bruno ^[3] ; Cardoso, Josiane de Oliveira ^[1] ; Oliveira, Regina Vincenzi ^[1] ; Forim, Moacir Rossi ^[1] ; Carneiro, Renato Lajarim ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Parana, Dept Chem, BR-81530900 Curitiba, Parana - Brazil

^[3] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 - USA

• Document type: Journal article
• Source: European Journal of Pharmaceutical Sciences; v. 165, OCT 1 2021.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 17/13095-0 - Experimental design applied to forced degradation of Nitazoxanide and Sofosbuvir pharmaceutical drugs
• Grantee: Benedito Roberto de Alvarenga Junior
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/16520-5 - Application of calibration chemometrics methods and multivariate curve resolution in Raman spectroscopy for qualitative, quantitative and polymorphism analyses in medicines
• Grantee: Renato Lajarim Carneiro
• Support Opportunities: Regular Research Grants