Publication detail

A critical review on thermodynamic and hydrodynamic modeling and simulation of liquid antisolvent crystallization of pharmaceutical compounds

Thakur, A.K. Kumar, R. Vipin, K.V.K. Kumar, A. Kumar G.G. Naresh, G.K.

English title

A critical review on thermodynamic and hydrodynamic modeling and simulation of liquid antisolvent crystallization of pharmaceutical compounds

Type

journal article in Web of Science

Language

en

Original abstract

Fine particles are in great demand in the pharmaceutical industry due to their versatile applications. Liquid antisolvent crystallization (LASC) is one of the promising approaches to prepare fine particles without requiring high energy. The interdependence of system thermodynamics, mass transfer kinetics, and the multi-phase hydrodynamics in the liquid antisolvent crystallization process is not well understood. In this review, the different modeling aspects of LASC are described from a fundamental perspective. The system thermodynamics of LASC is discussed and several models used in literature to predict the solubility in pure solvents and binary solvent mixtures are summarized. A detailed description of supersaturation, metastable zone width and induction time in antisolvent crystallization are presented and critically analyzed. The nucleation and growth kinetics are discussed and interpreted in terms of process variables. The hydrodynamic aspect of LASC which involves the mixing at different length scales is discussed and analyzed in detail. The CFD simulation-based approach to describe the interaction among different phenomena is critically reviewed. The crystallization scale-up, which is a major challenge in the LASC process, is discussed. A guideline for crystallization scale-up using the CFD-based modeling approach is presented which will be helpful to prospective researchers.

English abstract

Fine particles are in great demand in the pharmaceutical industry due to their versatile applications. Liquid antisolvent crystallization (LASC) is one of the promising approaches to prepare fine particles without requiring high energy. The interdependence of system thermodynamics, mass transfer kinetics, and the multi-phase hydrodynamics in the liquid antisolvent crystallization process is not well understood. In this review, the different modeling aspects of LASC are described from a fundamental perspective. The system thermodynamics of LASC is discussed and several models used in literature to predict the solubility in pure solvents and binary solvent mixtures are summarized. A detailed description of supersaturation, metastable zone width and induction time in antisolvent crystallization are presented and critically analyzed. The nucleation and growth kinetics are discussed and interpreted in terms of process variables. The hydrodynamic aspect of LASC which involves the mixing at different length scales is discussed and analyzed in detail. The CFD simulation-based approach to describe the interaction among different phenomena is critically reviewed. The crystallization scale-up, which is a major challenge in the LASC process, is discussed. A guideline for crystallization scale-up using the CFD-based modeling approach is presented which will be helpful to prospective researchers.

Keywords in English

CFD; Hydrodynamics; Liquid antisolvent crystallization; Scale-up; Solubility; Supersaturation

Released

15.09.2022

Publisher

Elsevier B.V.

ISSN

0167-7322

Number

362

Pages from–to

119663–119663

Pages count

17

BIBTEX


@article{BUT178541,
  author="Gajendra Kumar {Gaurav},
  title="A critical review on thermodynamic and hydrodynamic modeling and simulation of liquid antisolvent crystallization of pharmaceutical compounds",
  year="2022",
  number="362",
  month="September",
  pages="119663--119663",
  publisher="Elsevier B.V.",
  issn="0167-7322"
}