The impact of paracetamol impurities on face-specific properties: investigating the surface of single crystals using TOF-SIMS

Research output: Contribution to conferenceAbstract

Abstract

Understanding the mechanism of interaction between pharmaceutical molecules (API’s) and impurities on a crystal surfaces is key concept in understanding purification and designing pharmaceutical crystallization processes.
Different techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) that provide detailed imaging or elemental surface characterization. However, for studying molecular mechanisms of interaction time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identification and distribution. A primary ion pulse is accelerated and focused on the sample surface under ultra-high vacuum to emit secondary particles from the crystal surface. The emitted particles comprise; molecules, fragments of molecules and atoms. Analyzing these secondary particles provides information about the molecular and elemental species present on the surface.
By combining TOF-SIMS, SEM and OM analysis we can determine the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. The added value of this surface characterization technique is to understand the interactions between different molecular species during purification. 4-nitrophenol has been selected as an impurity which can be incorporated during crystallization of acetaminophen (paracetamol). Our study explores the distribution of impurity concentration on the different crystal faces of samples obtained by cooling crystallization over a range of impurity loadings and supersaturation conditions.
HPLC, Raman spectroscopy and single crystal XRD are used to verify the overall impurity presence and concentration and to confirm the identity of the crystal faces investigated.

Fingerprint

Secondary Ion Mass Spectrometry
Surface Properties
Acetaminophen
Secondary ion mass spectrometry
Crystallization
Single crystals
Impurities
Electron Scanning Microscopy
Crystals
Pharmaceutical Preparations
Photoelectron Spectroscopy
Drug products
Raman Spectrum Analysis
Vacuum
Molecules
Purification
High Pressure Liquid Chromatography
Ions
Scanning electron microscopy
Supersaturation

Keywords

  • ToF SIMS
  • single crystal
  • paracetamol
  • 4-nitrophenol
  • chemical characterisation
  • morphology

Cite this

@conference{56dd1a28201b40e5bc66a3bfc5a93714,
title = "The impact of paracetamol impurities on face-specific properties: investigating the surface of single crystals using TOF-SIMS",
abstract = "Understanding the mechanism of interaction between pharmaceutical molecules (API’s) and impurities on a crystal surfaces is key concept in understanding purification and designing pharmaceutical crystallization processes.Different techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) that provide detailed imaging or elemental surface characterization. However, for studying molecular mechanisms of interaction time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identification and distribution. A primary ion pulse is accelerated and focused on the sample surface under ultra-high vacuum to emit secondary particles from the crystal surface. The emitted particles comprise; molecules, fragments of molecules and atoms. Analyzing these secondary particles provides information about the molecular and elemental species present on the surface.By combining TOF-SIMS, SEM and OM analysis we can determine the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. The added value of this surface characterization technique is to understand the interactions between different molecular species during purification. 4-nitrophenol has been selected as an impurity which can be incorporated during crystallization of acetaminophen (paracetamol). Our study explores the distribution of impurity concentration on the different crystal faces of samples obtained by cooling crystallization over a range of impurity loadings and supersaturation conditions.HPLC, Raman spectroscopy and single crystal XRD are used to verify the overall impurity presence and concentration and to confirm the identity of the crystal faces investigated.",
keywords = "ToF SIMS, single crystal, paracetamol, 4-nitrophenol, chemical characterisation, morphology",
author = "Sara Ottoboni and Michael Chrubasik and {Mir Bruce}, Layla and Nguyen, {Thai Thu Hien} and Blair Johnston and Alastair Florence and Price, {Chris John}",
year = "2016",
month = "6",
day = "28",
language = "English",
note = "Crystal Growth of Organic Materials, CGOM ; Conference date: 26-06-2016 Through 30-06-2016",
url = "http://www.crystalgrowth2016.co.uk/wp-content/uploads/2016/06/CGOM-Conference-Programme.pdf",

}

The impact of paracetamol impurities on face-specific properties : investigating the surface of single crystals using TOF-SIMS. / Ottoboni, Sara; Chrubasik, Michael; Mir Bruce, Layla; Nguyen, Thai Thu Hien; Johnston, Blair; Florence, Alastair; Price, Chris John.

2016. Abstract from Crystal Growth of Organic Materials, Leeds, United Kingdom.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - The impact of paracetamol impurities on face-specific properties

T2 - investigating the surface of single crystals using TOF-SIMS

AU - Ottoboni, Sara

AU - Chrubasik, Michael

AU - Mir Bruce, Layla

AU - Nguyen, Thai Thu Hien

AU - Johnston, Blair

AU - Florence, Alastair

AU - Price, Chris John

PY - 2016/6/28

Y1 - 2016/6/28

N2 - Understanding the mechanism of interaction between pharmaceutical molecules (API’s) and impurities on a crystal surfaces is key concept in understanding purification and designing pharmaceutical crystallization processes.Different techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) that provide detailed imaging or elemental surface characterization. However, for studying molecular mechanisms of interaction time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identification and distribution. A primary ion pulse is accelerated and focused on the sample surface under ultra-high vacuum to emit secondary particles from the crystal surface. The emitted particles comprise; molecules, fragments of molecules and atoms. Analyzing these secondary particles provides information about the molecular and elemental species present on the surface.By combining TOF-SIMS, SEM and OM analysis we can determine the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. The added value of this surface characterization technique is to understand the interactions between different molecular species during purification. 4-nitrophenol has been selected as an impurity which can be incorporated during crystallization of acetaminophen (paracetamol). Our study explores the distribution of impurity concentration on the different crystal faces of samples obtained by cooling crystallization over a range of impurity loadings and supersaturation conditions.HPLC, Raman spectroscopy and single crystal XRD are used to verify the overall impurity presence and concentration and to confirm the identity of the crystal faces investigated.

AB - Understanding the mechanism of interaction between pharmaceutical molecules (API’s) and impurities on a crystal surfaces is key concept in understanding purification and designing pharmaceutical crystallization processes.Different techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) that provide detailed imaging or elemental surface characterization. However, for studying molecular mechanisms of interaction time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identification and distribution. A primary ion pulse is accelerated and focused on the sample surface under ultra-high vacuum to emit secondary particles from the crystal surface. The emitted particles comprise; molecules, fragments of molecules and atoms. Analyzing these secondary particles provides information about the molecular and elemental species present on the surface.By combining TOF-SIMS, SEM and OM analysis we can determine the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. The added value of this surface characterization technique is to understand the interactions between different molecular species during purification. 4-nitrophenol has been selected as an impurity which can be incorporated during crystallization of acetaminophen (paracetamol). Our study explores the distribution of impurity concentration on the different crystal faces of samples obtained by cooling crystallization over a range of impurity loadings and supersaturation conditions.HPLC, Raman spectroscopy and single crystal XRD are used to verify the overall impurity presence and concentration and to confirm the identity of the crystal faces investigated.

KW - ToF SIMS

KW - single crystal

KW - paracetamol

KW - 4-nitrophenol

KW - chemical characterisation

KW - morphology

UR - http://www.crystalgrowth2016.co.uk/

M3 - Abstract

ER -