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

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.

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.

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).

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.