58
H. Takiyama
Fig. 3.4 Operation point for
controlling polymorphism in
anti-solvent crystallization
0.1
0.2
0.3
0.1
0.2
0.3
0.4
0.5
0
Anti-solvent Conc. C Ant
Solute Concentration C
Changes in Soln. Conc.
passing through the anti-solvent apex. Then, crystals deposit and solution composition move downward along the straight line which connects the apex of solute.
Finally, solution composition moves in the direction of the lower right (point E). In
this way, the traveling rate of operation point (solution composition) is decided by
the addition rate of an anti-solvent, and the deposition rate of crystals [8, 9]. That
is, the trajectory of operation point on a phase diagram is decided by the addition
rate of an anti-solvent, and the deposition rate of crystals. Therefore, an operation
design can be achieved if the solubility of the three-component system [10] is known
in polymorph control of anti-solvent crystallization [5].
3.4 Controlling Polymorphism in Anti-solvent
Crystallization
In order to select the suitable operating conditions for controlling polymorph formation in anti-solvent crystallization is difficult because a particular polymorph may
precipitate at limited temperature and solvent composition [11, 12]. The crystallization behavior of polymorphous crystals depends on the anti-solvent addition rate
and the initial concentration of the solution in the anti-solvent crystallization [7].
These phenomena were explained with operation point trajectory in phase diagram
in which the stability regions of each polymorph were described. So it is necessary
to determine the operating conditions such as anti-solvent feed rate for controlling polymorph formation. If several kinds of polymorph crystals precipitate and
the target polymorph crystal is the stable form, the solvent-mediated transformation of metastable polymorph crystals must be completely suppressed in order to
avoid contamination. To obtain only desired stable polymorph, it is required not to
be precipitated metastable polymorph crystals. In the anti-solvent crystallization,
H. Takiyama
Fig. 3.4 Operation point for
controlling polymorphism in
anti-solvent crystallization
0.1
0.2
0.3
0.1
0.2
0.3
0.4
0.5
0
Anti-solvent Conc. C Ant
Solute Concentration C
Changes in Soln. Conc.
passing through the anti-solvent apex. Then, crystals deposit and solution composition move downward along the straight line which connects the apex of solute.
Finally, solution composition moves in the direction of the lower right (point E). In
this way, the traveling rate of operation point (solution composition) is decided by
the addition rate of an anti-solvent, and the deposition rate of crystals [8, 9]. That
is, the trajectory of operation point on a phase diagram is decided by the addition
rate of an anti-solvent, and the deposition rate of crystals. Therefore, an operation
design can be achieved if the solubility of the three-component system [10] is known
in polymorph control of anti-solvent crystallization [5].
3.4 Controlling Polymorphism in Anti-solvent
Crystallization
In order to select the suitable operating conditions for controlling polymorph formation in anti-solvent crystallization is difficult because a particular polymorph may
precipitate at limited temperature and solvent composition [11, 12]. The crystallization behavior of polymorphous crystals depends on the anti-solvent addition rate
and the initial concentration of the solution in the anti-solvent crystallization [7].
These phenomena were explained with operation point trajectory in phase diagram
in which the stability regions of each polymorph were described. So it is necessary
to determine the operating conditions such as anti-solvent feed rate for controlling polymorph formation. If several kinds of polymorph crystals precipitate and
the target polymorph crystal is the stable form, the solvent-mediated transformation of metastable polymorph crystals must be completely suppressed in order to
avoid contamination. To obtain only desired stable polymorph, it is required not to
be precipitated metastable polymorph crystals. In the anti-solvent crystallization,