| Autor: |
Bouchema TSE; Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, France., Annereau M; Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, France.; Clinical Pharmacy Department, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, 94800 Villejuif, France., Vieillard V; Department of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, France., Boquet R; Department of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, France., Coelho GA; Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, France., Castelli F; Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, CEA, INRAE, Université Paris-Saclay, 91191 Gif-sur-Yvette, France., Solgadi A; Ingénierie et Plateformes au Service de l'Innovation Thérapeutique, Inserm, CNRS, Université Paris-Saclay, 92296 Châtenay-Malabry, France., Paul M; Department of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, France.; EpidermE, Université Paris Est Creteil, 94010 Creteil, France., Yagoubi N; Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, France., Secretan PH; Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, France., Do B; Matériaux et Santé, Université Paris-Saclay, 91400 Orsay, France.; Department of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Créteil, France. |
| Abstrakt: |
Selumetinib is administered orally in capsule form and is indicated for the treatment of neurofibromatosis. To facilitate dosage adjustments, liquid preparations, such as solutions or suspensions, are to be developed. This led, first, to determine the stability profile of soluble or dispersed selumetinib and, secondly, to look for ways to stabilize the active substance. The degradation kinetics of selumetinib as a function of stress conditions were determined and compared. The degradation products were detected and identified by LC-HRMS n . In solution, selumetinib is sensitive to oxidation and degrades by photooxidation. In both cases, the side chain represented by the oxoamide group is concerned, leading to the formation of an amide derivative for the first case and an ester derivative for the second. The identification of such degradation mechanisms allowed us to study, in a targeted way, processes aiming at stabilizing the active molecule. |
