Chapter 5
Control of Crystal Size Distribution
and Polymorphs in the Crystallization
of Organic Compounds
Koichi Igarashi and Hiroshi Ooshima
Abstract Many of organic compounds, such as pharmaceuticals and chemicals, are
produced as crystals. Controlling the characteristics of these crystal products with
good reproducibility is essential for crystallization of organic compounds. There are
various characteristics to be controlled, such as grain size and distribution, crystal
polymorphism, crystal habit, and purity, but grain size and crystal polymorphism
are particularly essential characteristics. In order to control them, the authors have
developed several new crystallizers. This chapter highlights some recent crystallizers
to produce organic crystals with high quality.
Keywords Crystal property · Size distribution · Polymorphs
5.1 Introduction
5.1.1 Crystallization of Organic Compounds
Crystallization is one of the important unit operations of separation and purification
processes widely used in the production of pharmaceuticals, chemical products,
foods, etc. Since the product substance is recovered as a solid-state, solid–liquid
separation is possible by filtration, and the subsequent separation operation becomes
easy. Also, since the molecules are regularly arranged in the crystal, the products
with a high-purity can be obtained. The crystallization is generally considered to be
a low energy consuming process in the unit operation.
Generally, the drugs contain an active pharmaceutical ingredient (API) as a solid
(crystal), so crystallization is an important process. In particular, since the quality
of the API crystal as the final product also affects the drug efficacy in the body,
special care must be taken to control various crystal properties. For example, in the
K. Igarashi (B)
Graduate School of Engineering, Osaka City University, Osaka, Japan
e-mail: igarashi@osaka-cu.ac.jp
H. Ooshima
Kansai Chemical Engineering Co. Ltd., Amagasaki, Hyogo, Japan
© Springer Nature Singapore Pte Ltd. 2020
M. Sakamoto and H. Uekusa (eds.), Advances in Organic Crystal Chemistry,
https://doi.org/10.1007/978-981-15-5085-0_5
81
Control of Crystal Size Distribution
and Polymorphs in the Crystallization
of Organic Compounds
Koichi Igarashi and Hiroshi Ooshima
Abstract Many of organic compounds, such as pharmaceuticals and chemicals, are
produced as crystals. Controlling the characteristics of these crystal products with
good reproducibility is essential for crystallization of organic compounds. There are
various characteristics to be controlled, such as grain size and distribution, crystal
polymorphism, crystal habit, and purity, but grain size and crystal polymorphism
are particularly essential characteristics. In order to control them, the authors have
developed several new crystallizers. This chapter highlights some recent crystallizers
to produce organic crystals with high quality.
Keywords Crystal property · Size distribution · Polymorphs
5.1 Introduction
5.1.1 Crystallization of Organic Compounds
Crystallization is one of the important unit operations of separation and purification
processes widely used in the production of pharmaceuticals, chemical products,
foods, etc. Since the product substance is recovered as a solid-state, solid–liquid
separation is possible by filtration, and the subsequent separation operation becomes
easy. Also, since the molecules are regularly arranged in the crystal, the products
with a high-purity can be obtained. The crystallization is generally considered to be
a low energy consuming process in the unit operation.
Generally, the drugs contain an active pharmaceutical ingredient (API) as a solid
(crystal), so crystallization is an important process. In particular, since the quality
of the API crystal as the final product also affects the drug efficacy in the body,
special care must be taken to control various crystal properties. For example, in the
K. Igarashi (B)
Graduate School of Engineering, Osaka City University, Osaka, Japan
e-mail: igarashi@osaka-cu.ac.jp
H. Ooshima
Kansai Chemical Engineering Co. Ltd., Amagasaki, Hyogo, Japan
© Springer Nature Singapore Pte Ltd. 2020
M. Sakamoto and H. Uekusa (eds.), Advances in Organic Crystal Chemistry,
https://doi.org/10.1007/978-981-15-5085-0_5
81