In situ monitoring of stirring effects on polymorphic transformations during cooling crystallization of carbamazepine

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Abstract

The influence of experimental conditions on polymorphic outcome and transformations during cooling crystallization of carbamazepine (CBZ) from anhydrous ethanol has been investigated. Stirring was found to be the most important controlling factor for the initial polymorphic outcome in solutions prepared using commercial CBZ powder. For quiescent conditions, a few large crystals of the metastable trigonal α form (II) initially appeared, undergoing subsequent slow transformation into the stable P-monoclinic β form (III). Under sufficiently vigorous stirring, the induction times observed were clearly defined by the onset of turbidity, which was due to formation of a large number of small form III prismatic crystals. In experiments with solutions prepared by using recrystallized CBZ, significantly shorter induction times were observed under stirring conditions: a large number of small form II needle-shaped crystals initially formed at the onset of turbidity and then relatively rapidly transformed to small crystals of form III. This indicates a possible effect of impurities in the commercial CBZ powder inhibiting rapid nucleation of form II under stirring conditions. In situ monitoring of CBZ polymorphic outcome was performed using custom-built experimental setup for simultaneous measurement of intensity of transmitted and scattered light. Distinct pathways in two-variable intensity plots were observed for formation of each respective polymorph under stirring conditions. The same monitoring technique should be readily applicable to other systems.
LanguageEnglish
Pages4821-4828
Number of pages8
JournalCrystal Growth and Design
Volume12
Issue number10
DOIs
Publication statusPublished - 12 Sep 2012

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Carbamazepine
stirring
Crystallization
crystallization
Cooling
cooling
Crystals
Monitoring
Turbidity
turbidity
Powders
crystals
induction
Polymorphism
Needles
Ethanol
Nucleation
needles
Impurities
ethyl alcohol

Keywords

  • polymorphic outcome
  • crystallization of carbamazepine
  • stirring
  • CBZ
  • crystal formation

Cite this

@article{73ef0d53344142a98b41a548c0218387,
title = "In situ monitoring of stirring effects on polymorphic transformations during cooling crystallization of carbamazepine",
abstract = "The influence of experimental conditions on polymorphic outcome and transformations during cooling crystallization of carbamazepine (CBZ) from anhydrous ethanol has been investigated. Stirring was found to be the most important controlling factor for the initial polymorphic outcome in solutions prepared using commercial CBZ powder. For quiescent conditions, a few large crystals of the metastable trigonal α form (II) initially appeared, undergoing subsequent slow transformation into the stable P-monoclinic β form (III). Under sufficiently vigorous stirring, the induction times observed were clearly defined by the onset of turbidity, which was due to formation of a large number of small form III prismatic crystals. In experiments with solutions prepared by using recrystallized CBZ, significantly shorter induction times were observed under stirring conditions: a large number of small form II needle-shaped crystals initially formed at the onset of turbidity and then relatively rapidly transformed to small crystals of form III. This indicates a possible effect of impurities in the commercial CBZ powder inhibiting rapid nucleation of form II under stirring conditions. In situ monitoring of CBZ polymorphic outcome was performed using custom-built experimental setup for simultaneous measurement of intensity of transmitted and scattered light. Distinct pathways in two-variable intensity plots were observed for formation of each respective polymorph under stirring conditions. The same monitoring technique should be readily applicable to other systems.",
keywords = "polymorphic outcome, crystallization of carbamazepine, stirring, CBZ, crystal formation",
author = "Katarzyna Sypek and Iain Burns and Florence, {Alastair J.} and Jan Sefcik",
year = "2012",
month = "9",
day = "12",
doi = "10.1021/cg3005689",
language = "English",
volume = "12",
pages = "4821--4828",
journal = "Crystal Growth and Design",
issn = "1528-7483",
publisher = "American Chemical Society",
number = "10",

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TY - JOUR

T1 - In situ monitoring of stirring effects on polymorphic transformations during cooling crystallization of carbamazepine

AU - Sypek, Katarzyna

AU - Burns, Iain

AU - Florence, Alastair J.

AU - Sefcik, Jan

PY - 2012/9/12

Y1 - 2012/9/12

N2 - The influence of experimental conditions on polymorphic outcome and transformations during cooling crystallization of carbamazepine (CBZ) from anhydrous ethanol has been investigated. Stirring was found to be the most important controlling factor for the initial polymorphic outcome in solutions prepared using commercial CBZ powder. For quiescent conditions, a few large crystals of the metastable trigonal α form (II) initially appeared, undergoing subsequent slow transformation into the stable P-monoclinic β form (III). Under sufficiently vigorous stirring, the induction times observed were clearly defined by the onset of turbidity, which was due to formation of a large number of small form III prismatic crystals. In experiments with solutions prepared by using recrystallized CBZ, significantly shorter induction times were observed under stirring conditions: a large number of small form II needle-shaped crystals initially formed at the onset of turbidity and then relatively rapidly transformed to small crystals of form III. This indicates a possible effect of impurities in the commercial CBZ powder inhibiting rapid nucleation of form II under stirring conditions. In situ monitoring of CBZ polymorphic outcome was performed using custom-built experimental setup for simultaneous measurement of intensity of transmitted and scattered light. Distinct pathways in two-variable intensity plots were observed for formation of each respective polymorph under stirring conditions. The same monitoring technique should be readily applicable to other systems.

AB - The influence of experimental conditions on polymorphic outcome and transformations during cooling crystallization of carbamazepine (CBZ) from anhydrous ethanol has been investigated. Stirring was found to be the most important controlling factor for the initial polymorphic outcome in solutions prepared using commercial CBZ powder. For quiescent conditions, a few large crystals of the metastable trigonal α form (II) initially appeared, undergoing subsequent slow transformation into the stable P-monoclinic β form (III). Under sufficiently vigorous stirring, the induction times observed were clearly defined by the onset of turbidity, which was due to formation of a large number of small form III prismatic crystals. In experiments with solutions prepared by using recrystallized CBZ, significantly shorter induction times were observed under stirring conditions: a large number of small form II needle-shaped crystals initially formed at the onset of turbidity and then relatively rapidly transformed to small crystals of form III. This indicates a possible effect of impurities in the commercial CBZ powder inhibiting rapid nucleation of form II under stirring conditions. In situ monitoring of CBZ polymorphic outcome was performed using custom-built experimental setup for simultaneous measurement of intensity of transmitted and scattered light. Distinct pathways in two-variable intensity plots were observed for formation of each respective polymorph under stirring conditions. The same monitoring technique should be readily applicable to other systems.

KW - polymorphic outcome

KW - crystallization of carbamazepine

KW - stirring

KW - CBZ

KW - crystal formation

UR - http://pubs.acs.org/journal/cgdefu

U2 - 10.1021/cg3005689

DO - 10.1021/cg3005689

M3 - Article

VL - 12

SP - 4821

EP - 4828

JO - Crystal Growth and Design

T2 - Crystal Growth and Design

JF - Crystal Growth and Design

SN - 1528-7483

IS - 10

ER -