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H. Rehage and M. Kind
Abbreviations
BF
Bulk fluid
CFD
Computational fluid dynamics
CIJM
Confined impinging jet mixer
STR
Stirred-tank reactor
DLS
Dynamic light scattering
E-model Engulfment model
MSMPR Mixed-suspension, mixed product-removal
JICF
Jet in cross flow
PBE
Population balance equation
PFR
Plug flow reactor
PSD
Particle size distribution
SEM
Scanning electron microscopy
SLS
Static light scattering
Dimensionless Numbers
Sh
Sherwood number [–]
1 Introduction
Precipitation is an important solids formation process which is extensively applied in
the chemical and pharmaceutical industry. Among the products typically produced
by precipitation are active pharmaceutical ingredients, color pigments and catalyst
materials. Sparingly soluble salts are a specific class of material which pose a serious
challenge for industrial process development. They are often precipitated by mixing
two aqueous salt solutions, each of them carrying one of the reactive ion types. Due
to the low product solubility in the mixture, solid formation is triggered after mixing
both educts. As the supersaturation reached for sparingly soluble salt precipitation is
generally on a high level compared to other crystallization processes, the increased
nucleation and growth rates cause a small time scale of solids formation τ sf [s]. If
τ mix /τ sf ≥ 1 with τ mix [s] designating the time scale of mixing, the latter can crucially
influence the PSD of the solid product. As consecutive process steps, such as centrifugation, rely heavily on the product PSD, knowledge about the process functionality
between process parameters and the PSD is required for process development.
The standard apparatus for technical precipitation is the STR in batch, semi-batch
or continuous operation mode. The semi-batch operation is often the method of
choice, especially for fine chemical products, as flexible production is possible here.
A central drawback of the semi-batch operation, besides the process dynamics, is
H. Rehage and M. Kind
Abbreviations
BF
Bulk fluid
CFD
Computational fluid dynamics
CIJM
Confined impinging jet mixer
STR
Stirred-tank reactor
DLS
Dynamic light scattering
E-model Engulfment model
MSMPR Mixed-suspension, mixed product-removal
JICF
Jet in cross flow
PBE
Population balance equation
PFR
Plug flow reactor
PSD
Particle size distribution
SEM
Scanning electron microscopy
SLS
Static light scattering
Dimensionless Numbers
Sh
Sherwood number [–]
1 Introduction
Precipitation is an important solids formation process which is extensively applied in
the chemical and pharmaceutical industry. Among the products typically produced
by precipitation are active pharmaceutical ingredients, color pigments and catalyst
materials. Sparingly soluble salts are a specific class of material which pose a serious
challenge for industrial process development. They are often precipitated by mixing
two aqueous salt solutions, each of them carrying one of the reactive ion types. Due
to the low product solubility in the mixture, solid formation is triggered after mixing
both educts. As the supersaturation reached for sparingly soluble salt precipitation is
generally on a high level compared to other crystallization processes, the increased
nucleation and growth rates cause a small time scale of solids formation τ sf [s]. If
τ mix /τ sf ≥ 1 with τ mix [s] designating the time scale of mixing, the latter can crucially
influence the PSD of the solid product. As consecutive process steps, such as centrifugation, rely heavily on the product PSD, knowledge about the process functionality
between process parameters and the PSD is required for process development.
The standard apparatus for technical precipitation is the STR in batch, semi-batch
or continuous operation mode. The semi-batch operation is often the method of
choice, especially for fine chemical products, as flexible production is possible here.
A central drawback of the semi-batch operation, besides the process dynamics, is