Product Quality and Polymorphism

The formation of polymorphs and various hydrates can also affect many quality factors and must be carefully considered in stability criteria (Pikal, 1999b Morris et al, 2001). Many experimental results have shown that crystallization from aqueous solutions is favored by higher concentrations of crystallizable solute. On the contrary, the presence of high concentrations of other solutes that remain amorphous generally prevents the crystallization of the main possible crystallizable solute. For example, the crystallization of mannitol, which is easy if this solute is quite pure, becomes improbable in the presence of other solutes in high concentration. 

Consequently, a common effort should be made to establish and complete the data basis concerning the numerous thermodynamic, thermophysical, transport and rheological properties necessary for modeling and simulating the different steps of this complex mild drying process. Moreover, the methods available for the characterization of most of these end-use properties should be improved and additional characterization methods should be adapted from other research fields (material science, applied biochemistry, physical chemistry, etc.). Improved characterization methods promise a better description and a safer control of numerous end-use properties for existing freeze-dryers as well as for new machines with more possibilities to better comply with more and more severe quality requirements in the future. The use of non-invasive sensors or of rapid non-intrusive methods for on-line and in situ estimation of the main parameters of the process could also help to overcome the difficulties observed, for example, the artifacts resulting from invasive sensors inserted inside vials and presently commonly used. 

Rp water (solvent) vapor mass transfer resistance Pa m s hg  

API active principle ingredient BSA bovine serum albumin DSC differential scanning microscopy FTIR Fourier transform infra-red IR infra-red 

MDSC modulated scanning microscopy MTM manometric temperature measurement NMR nuclear magnetic resonance PAR pressure rise analysis US ultrasound 

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