Summary We address the novel Bayesian treatment of design space for a lyophilized parenteral. The system studied was sodium ethacrynate (Mockus L, Paul, TW, Pease, NA, et al. Quality by Design in Formulation and Process Development for a Freeze-dried, Small Molecule Parenteral Product: A Case Study. Pharmaceutical Development and Technology. 2011; 16(6): 549?576). Sodium ethacrynate was formed in aqueous solution by titration of ethacrynic acid with 1?N sodium hydroxide solution. Immediately after completion of titration in order to prevent degradation in the liquid state, the pre-lyo solution was freeze-dried. After completion of freeze-drying, stoppered vials containing freeze-dried cake were stored under constant conditions of 30 and 40?°C to collect stability data. It was found that the shelf life stability of the lyophilized product is affected by formulation parameters such as pH, API, and buffer concentration. The Bayesian approach naturally aligns with the ICH Q8 definition of design space. Moreover, it is more intuitive and useful than the traditional point estimate design space representation. The proposed approach also provides estimates of risk of failure of product attributes such as shelf life and activation energy.
- Design Space