3 Anti-solvent Crystallization Method for Production …
57
Temperature
Concentration
Q
R
M
Fig. 3.2 Solution-mediated polymorph transformation
is supersaturation condition for Form II. If the nucleation of Form II occurs here,
crystallization of Form II starts and solution concentration decreases. Since, the solution becomes undersaturated for Form I, Form I which already deposited dissolves.
Therefore, in the region between solubility curves, solution-mediated transformation
occurs as shown in Fig. 3.3.
Anti-solvent crystallization method is also important for the control of crystal
polymorph [5] and morphology [6, 7]. Then, let’s consider the operation of antisolvent crystallization in which an operation point (solution concentration in ternary
phase diagram) does not exceed the solubility of metastable form in ternary phase
diagram. The example is explained in Fig. 3.4. If a pure anti-solvent is added in the
solution (point S), the solution composition moves to the right along the straight line
Plate Crystal : Dissolution of metastable form
Needle Crystal : Growth of stable form
Fig. 3.3 Changes in polymorph crystals during solution-mediated polymorph transformation
57
Temperature
Concentration
Q
R
M
Fig. 3.2 Solution-mediated polymorph transformation
is supersaturation condition for Form II. If the nucleation of Form II occurs here,
crystallization of Form II starts and solution concentration decreases. Since, the solution becomes undersaturated for Form I, Form I which already deposited dissolves.
Therefore, in the region between solubility curves, solution-mediated transformation
occurs as shown in Fig. 3.3.
Anti-solvent crystallization method is also important for the control of crystal
polymorph [5] and morphology [6, 7]. Then, let’s consider the operation of antisolvent crystallization in which an operation point (solution concentration in ternary
phase diagram) does not exceed the solubility of metastable form in ternary phase
diagram. The example is explained in Fig. 3.4. If a pure anti-solvent is added in the
solution (point S), the solution composition moves to the right along the straight line
Plate Crystal : Dissolution of metastable form
Needle Crystal : Growth of stable form
Fig. 3.3 Changes in polymorph crystals during solution-mediated polymorph transformation