Quality by design: optimization of a freeze-drying cycle via design space in case of heterogeneous drying behavior and influence of the freezing protocol.

Purpose: This paper shows how to optimize the primary drying phase, for both product quality and drying time, of a parenteral formulation via design space.

Methods: A non-steady state model, parameterized with experimentally determined heat and mass transfer coefficients, is used to define the design space when the heat transfer coefficient varies with the position of the vial in the array. The calculations recognize both equipment and product constraints, and also take into account model parameter uncertainty.