3 Anti-solvent Crystallization Method for Production …
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solute in the solution and crystal will be produced. This crystallization process is
often used especially in pharmaceutical industry.
The characteristics of anti-solvent crystallization are described as follows [1]:
(a) Operation at ambient temperature
This crystallization method is operated at ambient temperature and it is not
necessary to heat up or cool down the crystallizer in order for crystallization.
This will have huge benefits in terms of cost and expenditure. Additionally, it
is suitable for crystallization of heat-sensitive materials such as biomaterial and
pharmaceutical products. Moreover, crystallization of soluble materials whose
solubility is weak in temperature dependency can be carried out too.
(b) High yield in productivity
Just by adding the solution, supersaturation will be generated and crystal will
be produced within a shorter period of time. Besides that, in the case where
there is still solute dissolved in solution, adding more anti-solvent will help in
the solute recovery process.
(c) Unique product quality
Compared to cooling crystallization, wide attainability of supersaturation can
be achieved. With higher supersaturation, nucleation rate will increase and fine
crystals can be easily produced. However, with the generation of more fine
crystals, crystals will agglomerate and there will be difficulty in solid–liquid
separation process.
3.2.2 Ternary Phase Diagram
In order to further understand the anti-solvent crystallization process, it is easier to use
a ternary phase diagram. Considering a solute dissolved at an arbitrary temperature.
The solubility curve is shown in a ternary phase diagram as in Fig. 3.1. E (solute)–
B (original solvent)–A (anti-solvent) system is considered. Solution A is the antisolvent-rich solution and solution B is the original solvent-rich saturated solution.
When solution A and B with mass m A and m B are mix together the mass ratio will
become m A : m B = α:β from the principle of lever rule, and the apparent mix solution
will be at point M. Since solution M is supersaturated, crystals will be generated and
the composition of the solution will move to point S which is the equilibrium point.
Concentration difference, C can be express as
C = C 0 − C
∗
(3.1)
C
* represents the equilibrium concentration. Saturation ratio, S and Supersaturation ratio, σ can be written as
ln
C 0
C ∗ = lnS = ln
1 +
(C 0 − C
∗
)
C ∗
= ln
1 +
C
C ∗
= ln(1 + σ ) ∼ = σ (3.2)
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solute in the solution and crystal will be produced. This crystallization process is
often used especially in pharmaceutical industry.
The characteristics of anti-solvent crystallization are described as follows [1]:
(a) Operation at ambient temperature
This crystallization method is operated at ambient temperature and it is not
necessary to heat up or cool down the crystallizer in order for crystallization.
This will have huge benefits in terms of cost and expenditure. Additionally, it
is suitable for crystallization of heat-sensitive materials such as biomaterial and
pharmaceutical products. Moreover, crystallization of soluble materials whose
solubility is weak in temperature dependency can be carried out too.
(b) High yield in productivity
Just by adding the solution, supersaturation will be generated and crystal will
be produced within a shorter period of time. Besides that, in the case where
there is still solute dissolved in solution, adding more anti-solvent will help in
the solute recovery process.
(c) Unique product quality
Compared to cooling crystallization, wide attainability of supersaturation can
be achieved. With higher supersaturation, nucleation rate will increase and fine
crystals can be easily produced. However, with the generation of more fine
crystals, crystals will agglomerate and there will be difficulty in solid–liquid
separation process.
3.2.2 Ternary Phase Diagram
In order to further understand the anti-solvent crystallization process, it is easier to use
a ternary phase diagram. Considering a solute dissolved at an arbitrary temperature.
The solubility curve is shown in a ternary phase diagram as in Fig. 3.1. E (solute)–
B (original solvent)–A (anti-solvent) system is considered. Solution A is the antisolvent-rich solution and solution B is the original solvent-rich saturated solution.
When solution A and B with mass m A and m B are mix together the mass ratio will
become m A : m B = α:β from the principle of lever rule, and the apparent mix solution
will be at point M. Since solution M is supersaturated, crystals will be generated and
the composition of the solution will move to point S which is the equilibrium point.
Concentration difference, C can be express as
C = C 0 − C
∗
(3.1)
C
* represents the equilibrium concentration. Saturation ratio, S and Supersaturation ratio, σ can be written as
ln
C 0
C ∗ = lnS = ln
1 +
(C 0 − C
∗
)
C ∗
= ln
1 +
C
C ∗
= ln(1 + σ ) ∼ = σ (3.2)