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Modification of Drug Crystallization by Cyclodextrins in Pre-formulation Study.

Daisuke Iohara1,2, Makoto Anraku1,2, Kaneto Uekama1

  • 1Faculty of Pharmaceutical Sciences, Sojo University.

Chemical & Pharmaceutical Bulletin
|September 3, 2019
PubMed
Summary

Hydrophilic cyclodextrins (CDs) control drug crystallization by altering pathways and modifying crystal habits. These additives enable the formation of stable amorphous drug/CDs complexes, advancing pre-formulation studies.

Keywords:
amorphouscrystal habitcyclodextrin (CD)polymorphsolid statesolution-mediated transition

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Area of Science:

  • Pharmaceutical Science
  • Materials Science
  • Physical Chemistry

Background:

  • Controlling drug crystallization is crucial in pre-formulation studies.
  • Advanced additives are increasingly used to manage drug crystallization behavior.
  • Hydrophilic cyclodextrins (CDs) are emerging as effective additives for this purpose.

Purpose of the Study:

  • To review the application of hydrophilic cyclodextrins (CDs) in controlling drug crystallization.
  • To explore the mechanisms by which CDs influence crystallization in solution and solid states.
  • To highlight the role of CDs in crystal engineering and amorphous formulation.

Main Methods:

  • Host-guest interactions between CDs and drug molecules.
  • Selective suppression of crystallization pathways.
  • Modification of crystal morphology (habit) through controlled growth.
  • Preparation of stable amorphous drug/CDs complexes.

Main Results:

  • CDs, through host-guest interactions, can suppress solution-mediated transitions, leading to selective precipitation of metastable drug forms.
  • CDs facilitate crystal engineering by altering crystallization pathways, enabling the discovery of new polymorphs.
  • CDs can modify crystal habit by selectively inhibiting growth in specific directions.
  • Stable amorphous drug/CDs complexes were prepared using specific CDs, even under humid conditions.

Conclusions:

  • Hydrophilic cyclodextrins are versatile additives for controlling drug crystallization processes.
  • CDs offer opportunities for polymorph discovery and crystal habit modification.
  • CDs are valuable in developing stable amorphous drug formulations.