Optimization of the lyophilisation process for esomeprazole 40 mg powder for solution for injection/infusion using quality by design concept

The aim of this work was to apply the of Quality by Design concept in optimization of lyophilisation process in production of esomeprazole 40 mg powder for solution for injection/infusion. Optimization has been triggered by the product solution's sensitivity to oxygen, which leads to a fast decrease in pH value and limits allowable duration of air exposure. Lyophilizer capacity and number of ‘’good’’ vials of finished product are thereby significantly reduced, presenting serious obstacle for scale-up from 17,000 vials to 33,000 vials. With goal to maintain pH stable during production of an almost twice as big batch, a pre-freezing phase after filling, and before lyophilisation was introduced. Starting from the Quality Target Product Profile, Failure mode and effects analysis (FMEA) was applied for the purpose of defining Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), Critical Quality Attributes (CQAs) and control strategy for the production. It was confirmed that temperature of shelfs of −30 °C, as opposed to 20 °C, significantly extends the time for which esomeprazole solution remains stable. Finally, an artificial neural network model was built and trained in order to define the design space for the lyophilisation process. It was demonstrated that the pH of esomeprazole solution remains stable and in specification within the lyophilizer's shelf temperature range of −10 °C to −30 °C for 5–26 h