Optimization of Primary Drying Time Using a Combination of ControLyo~(TM) Nucleation on Demand and SMART? Freeze Dryer Technology

摘要

Given significant costs of producing a freeze-dried product (including equipment, utilities, etc.) along with the desire to decrease development timelines to get products on the market faster, reducing cycle development times and shortening the drying cycles are two significant financial drivers in today's industry.Current conventional cycle development still consists of a trial and error methodology. Based on knowledge of the critical temperature of a formulation (glass transition, T', or collapse temperature, Tc), the goal is to narrowly control heat flow into the product to avoid the product temperature exceeding this critical formulation temperature. Exceeding this could lead to melting or collapse of the freeze-dried cake, which compromises the quality attributes of the final drug product. Heat is generally added by shelf temperature adjustment and the process requires the development scientist to make a small change to the shelf temperature, then wait and watch the impact on product temperature. This process is repeated until the scientist finds a shelf temperature resulting in a product temperature close to the critical formulation temperature, controlled typically about 3-5°C below this critical temperature boundary (safety margin). It is also important to not allow this safety margin to be too large, as for each 1 °C warmer the freeze dryer is run, primary drying can be reduced by up to 13%.