Formulation Challenges in Lyophilized Products
Formulation challenges in pharmaceuticals are increasing in complexity due to the rise of thermolabile and biopharmaceutical products, requiring a deep understanding of physicochemical processes and drug-excipient interactions. Freeze-drying is a widely used method to stabilize sensitive APIs such as pantoprazole sodium sesquihydrate, which presents cosmetic defects like cake cracking despite its chemical stability. This study, conducted by the Syntegon Telstar Process Laboratory, aimed to mitigate cracking through optimized formulation strategies using mannitol and trehalose in different ratios and processing conditions. Thermal analysis (DSC, FDM), crystallinity assessment (PXRD), and product characterization revealed that a 3:1 mannitol-to-trehalose ratio at 10% solid content with -10 °C annealing produced the most stable and visually acceptable formulation. This matrix favored- -mannitol crystallization and preserved trehalose in its amorphous state, minimizing polymorphic instability and improving cake structure. The findings underscore the importance of excipient selection and process design in achieving high-quality lyophilized pharmaceutical products.
