Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes

PURPOSE: Present (i) an infrared (IR)-based Process Analytical Technology (PAT) installed in a lab-scale freeze-dryer and (ii) a micro freeze-dryer (MicroFD®) as effective tools for freeze-drying design space calculation of the primary drying stage. METHODS: The case studies investigated are the freeze-drying of a crystalline (5% mannitol) and of an amorphous (5% sucrose) solution processed in 6R vials. The heat (K(v)) and the mass (R(p)) transfer coefficients were estimated: tests at 8, 13 and 26 Pa were carried out to assess the chamber pressure effect on K(v). The design space of the primary drying stage was calculated using these parameters and a well-established model-based approach. The results obtained using the proposed tools were compared to the ones in case K(v) and R(p) were estimated in a lab-scale unit through gravimetric tests and a thermocouple-based method, respectively. RESULTS: The IR-based method allows a non-gravimetric estimation of the K(v) values while with the micro freeze-dryer gravimetric tests require a very small number of vials. In both cases, the obtained values of K(v) and R(p), as well as the resulting design spaces, were all in very good agreement with those obtained in a lab-scale unit through the gravimetric tests (K(v)) and the thermocouple-based method (R(p)). CONCLUSIONS: The proposed tools can be effectively used for design space calculation in substitution of other well-spread methods. Their advantages are mainly the less laborious K(v) estimation process and, as far as the MicroFD® is concerned, the possibility of saving time and formulation material when evaluating R(p).