Abstract
PurposePresent (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.MethodsThe 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 (Kv) and the mass (Rp) transfer coefficients were estimated: tests at 8, 13 and 26 Pa were carried out to assess the chamber pressure effect on Kv. 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 Kv and Rp were estimated in a lab-scale unit through gravimetric tests and a thermocouple-based method, respectively.ResultsThe IR-based method allows a non-gravimetric estimation of the Kv values while with the micro freeze-dryer gravimetric tests require a very small number of vials. In both cases, the obtained values of Kv and Rp, 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 (Kv) and the thermocouple-based method (Rp).ConclusionsThe proposed tools can be effectively used for design space calculation in substitution of other well-spread methods. Their advantages are mainly the less laborious Kv estimation process and, as far as the MicroFD® is concerned, the possibility of saving time and formulation material when evaluating Rp.
Highlights
Freeze drying is a process widely used in the pharmaceutical industry to recover drug formulations from aqueous solutions
It can be appreciated that the resulting design spaces obtained through the different tested tools and approaches are all in good agreement
The industrial equipment should be tested at full capacity and different pressures as described in Patel et al [12]. This should be done just once and it can be used for all future process design for that piece of equipment. Both alternative methods investigated in this paper for design space estimation present advantages and limitations
Summary
Freeze drying is a process widely used in the pharmaceutical industry to recover drug formulations from aqueous solutions. First the solution is frozen, the pressure is lowered, and heat is supplied to promote sublimation of the solvent (primary drying). Freeze drying is a long and costly process, and is generally used over other drying methods when the drug formulation is heat sensitive [2]. Notwithstanding the price, it is estimated that 16% of the top-selling 100 pharmaceuticals are freezedried [3]. Is it imperative to have fast and efficient freeze-drying process development (and optimization) tools, shortening the time-to-market and providing benefits to the patients
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