Abstract
Current trends in the pharmaceutical industry led to a demand for more flexible manufacturing processes with smaller batch sizes. Prepackaged nested vials that can be processed as a unit were introduced into the market to fulfill this need. However, vial nests provide a different thermal environment for the vials compared to a hexagonal packaging array and could therefore influence product temperature profiles, primary drying times, and product quality attributes. Polymer caps with the possibility of vial closure inside the freeze-drying chamber were developed to remove the risks and need of a crimping process. A general concern with the use of such caps is the possibility of an increase in resistance to water vapor flow out of the vial. This case study investigated the effect of the LyoSeal® and PLASCAP® polymer caps and EZ-fill® nests on the freeze-drying process. Amorphous and partially crystalline model formulations were freeze-dried. Process data and product quality attributes were compared for regularly stoppered vials and vials with polymer caps as well as vials in a hexagonal packaging array and nested vials. The results indicated no increased resistance or impeded water vapor flow by the polymer caps. Differences in the macro- and microscopic appearances of products and a trend towards lower product temperatures were observed for the investigated nest type compared to a regular hexagonal packaging array. Consequently, the polymer caps could be used as an alternative to regular stoppers without affecting freeze-drying process data or product quality attributes, while the different thermal environment of nested vials should be considered.
Highlights
Freeze-drying is an integral manufacturing technique for the preparation and stabilization of parenteral drugs
50% of the approved biopharmaceutical drugs are processed by freeze-drying according to the US Food and Drug Association (FDA) and European Medicines Agency (EMA) [1]
Unfrozen water that is immobilized in the amorphous product matrix or adsorbed to the product surface is removed by diffusion and desorption during secondary drying by a further increase in Ts [2, 3]
Summary
Freeze-drying is an integral manufacturing technique for the preparation and stabilization of parenteral drugs. Stopper placement, and loading of the freeze-dryer, the freeze-drying process itself is performed in three steps. The product solution is completely solidified during the freezing step by reducing the shelf temperature (Ts) at atmospheric pressure. The chamber pressure is reduced to facilitate ice sublimation during primary drying. Ts is typically increased during this step to provide the energy required for sublimation while maintaining the product temperature below its critical formulation temperature to avoid cosmetic defects and quality issues. Unfrozen water that is immobilized in the amorphous product matrix or adsorbed to the product surface is removed by diffusion and desorption during secondary drying by a further increase in Ts [2, 3]. The vials are stoppered under vacuum within the freeze-drying chamber before unloading and capping them with an aluminum crimp
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