Oxcarbazepine form III: observation of twisted habit in crystals of an elusive pharmaceutical polymorph

H. Polyzois, R. Guo, M. Warzecha, S. L . Price, A.J. Florence

Research output: Contribution to conferencePoster

Abstract

Crystals exhibiting twisted habit have been observed at the nanoscale, mesoscale, and macroscale and pose challenges with respect to structural characterisation because of their lack of long-range translational symmetry [1]. Crystal structure prediction (CSP) investigations of an active pharmaceutical ingredient’s lattice energy landscape are a potent tool for assisting experimentalists in identifying and characterising novel polymorphic forms that are thermodynamically feasible, including ones that crystallise with twisted morphologies [2-4]. Oxcarbazepine (OXCBZ) is a pharmaceutical used for the treatment of epileptic seizures and three polymorphic forms have been reported, two of which (form I and form II) crystallise in the monoclinic space groups P21/c and P21 respectively [5]. OXCBZ form III was originally prepared by slow evaporation from methanol solutions containing polymer additives but structure determination was not possible because of the small size and poor quality of the crystals produced. Herein, we present robust protocols for the crystallisation of OXCBZ III from both solution and the vapour phase. Our efforts combined CSP studies of OXCBZ with physical vapour deposition and solution-based polymorph screening experiments. Needle-like and fibre-like crystals of form III exhibiting variable twisted habit were serendipitously obtained through vapour deposition of OXCBZ onto metallic substrates. By performing scanning electron and atomic force microscopy investigations we have managed to gain insight into the mechanism of formation and growth of the twisted OXCBZ III crystals over the course of the deposition process.

Conference

Conference50th Annual Conference of the British Association of Crystal Growth
CountryUnited Kingdom
CityLondon
Period9/07/1911/07/19

Fingerprint

Polymorphism
Drug products
Crystals
Pharmaceutical Preparations
Crystal structure
Vapor deposition
Crystal symmetry
Physical vapor deposition
Needles
Atomic force microscopy
Screening
Evaporation
Methanol
Crystallization
Vapors
Scanning
oxcarbazepine
Electrons
Fibers
Polymers

Keywords

  • oxcarbazepine
  • pharmaceutical polymorphism
  • crystal structure prediction
  • twisted crystal habit

Cite this

Polyzois, H., Guo, R., Warzecha, M., Price, S. L. ., & Florence, A. J. (2019). Oxcarbazepine form III: observation of twisted habit in crystals of an elusive pharmaceutical polymorph. 69. Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom.
Polyzois, H. ; Guo, R. ; Warzecha, M. ; Price, S. L . ; Florence, A.J. / Oxcarbazepine form III : observation of twisted habit in crystals of an elusive pharmaceutical polymorph. Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom.1 p.
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abstract = "Crystals exhibiting twisted habit have been observed at the nanoscale, mesoscale, and macroscale and pose challenges with respect to structural characterisation because of their lack of long-range translational symmetry [1]. Crystal structure prediction (CSP) investigations of an active pharmaceutical ingredient’s lattice energy landscape are a potent tool for assisting experimentalists in identifying and characterising novel polymorphic forms that are thermodynamically feasible, including ones that crystallise with twisted morphologies [2-4]. Oxcarbazepine (OXCBZ) is a pharmaceutical used for the treatment of epileptic seizures and three polymorphic forms have been reported, two of which (form I and form II) crystallise in the monoclinic space groups P21/c and P21 respectively [5]. OXCBZ form III was originally prepared by slow evaporation from methanol solutions containing polymer additives but structure determination was not possible because of the small size and poor quality of the crystals produced. Herein, we present robust protocols for the crystallisation of OXCBZ III from both solution and the vapour phase. Our efforts combined CSP studies of OXCBZ with physical vapour deposition and solution-based polymorph screening experiments. Needle-like and fibre-like crystals of form III exhibiting variable twisted habit were serendipitously obtained through vapour deposition of OXCBZ onto metallic substrates. By performing scanning electron and atomic force microscopy investigations we have managed to gain insight into the mechanism of formation and growth of the twisted OXCBZ III crystals over the course of the deposition process.",
keywords = "oxcarbazepine, pharmaceutical polymorphism, crystal structure prediction, twisted crystal habit",
author = "H. Polyzois and R. Guo and M. Warzecha and Price, {S. L .} and A.J. Florence",
year = "2019",
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note = "50th Annual Conference of the British Association of Crystal Growth ; Conference date: 09-07-2019 Through 11-07-2019",

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Polyzois, H, Guo, R, Warzecha, M, Price, SL & Florence, AJ 2019, 'Oxcarbazepine form III: observation of twisted habit in crystals of an elusive pharmaceutical polymorph' 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom, 9/07/19 - 11/07/19, pp. 69.

Oxcarbazepine form III : observation of twisted habit in crystals of an elusive pharmaceutical polymorph. / Polyzois, H.; Guo, R.; Warzecha, M.; Price, S. L .; Florence, A.J.

2019. 69 Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Oxcarbazepine form III

T2 - observation of twisted habit in crystals of an elusive pharmaceutical polymorph

AU - Polyzois, H.

AU - Guo, R.

AU - Warzecha, M.

AU - Price, S. L .

AU - Florence, A.J.

PY - 2019/7/9

Y1 - 2019/7/9

N2 - Crystals exhibiting twisted habit have been observed at the nanoscale, mesoscale, and macroscale and pose challenges with respect to structural characterisation because of their lack of long-range translational symmetry [1]. Crystal structure prediction (CSP) investigations of an active pharmaceutical ingredient’s lattice energy landscape are a potent tool for assisting experimentalists in identifying and characterising novel polymorphic forms that are thermodynamically feasible, including ones that crystallise with twisted morphologies [2-4]. Oxcarbazepine (OXCBZ) is a pharmaceutical used for the treatment of epileptic seizures and three polymorphic forms have been reported, two of which (form I and form II) crystallise in the monoclinic space groups P21/c and P21 respectively [5]. OXCBZ form III was originally prepared by slow evaporation from methanol solutions containing polymer additives but structure determination was not possible because of the small size and poor quality of the crystals produced. Herein, we present robust protocols for the crystallisation of OXCBZ III from both solution and the vapour phase. Our efforts combined CSP studies of OXCBZ with physical vapour deposition and solution-based polymorph screening experiments. Needle-like and fibre-like crystals of form III exhibiting variable twisted habit were serendipitously obtained through vapour deposition of OXCBZ onto metallic substrates. By performing scanning electron and atomic force microscopy investigations we have managed to gain insight into the mechanism of formation and growth of the twisted OXCBZ III crystals over the course of the deposition process.

AB - Crystals exhibiting twisted habit have been observed at the nanoscale, mesoscale, and macroscale and pose challenges with respect to structural characterisation because of their lack of long-range translational symmetry [1]. Crystal structure prediction (CSP) investigations of an active pharmaceutical ingredient’s lattice energy landscape are a potent tool for assisting experimentalists in identifying and characterising novel polymorphic forms that are thermodynamically feasible, including ones that crystallise with twisted morphologies [2-4]. Oxcarbazepine (OXCBZ) is a pharmaceutical used for the treatment of epileptic seizures and three polymorphic forms have been reported, two of which (form I and form II) crystallise in the monoclinic space groups P21/c and P21 respectively [5]. OXCBZ form III was originally prepared by slow evaporation from methanol solutions containing polymer additives but structure determination was not possible because of the small size and poor quality of the crystals produced. Herein, we present robust protocols for the crystallisation of OXCBZ III from both solution and the vapour phase. Our efforts combined CSP studies of OXCBZ with physical vapour deposition and solution-based polymorph screening experiments. Needle-like and fibre-like crystals of form III exhibiting variable twisted habit were serendipitously obtained through vapour deposition of OXCBZ onto metallic substrates. By performing scanning electron and atomic force microscopy investigations we have managed to gain insight into the mechanism of formation and growth of the twisted OXCBZ III crystals over the course of the deposition process.

KW - oxcarbazepine

KW - pharmaceutical polymorphism

KW - crystal structure prediction

KW - twisted crystal habit

UR - https://www.bacg.co.uk/bacg-50th-annual-conference/

M3 - Poster

SP - 69

ER -

Polyzois H, Guo R, Warzecha M, Price SL, Florence AJ. Oxcarbazepine form III: observation of twisted habit in crystals of an elusive pharmaceutical polymorph. 2019. Poster session presented at 50th Annual Conference of the British Association of Crystal Growth, London, United Kingdom.