Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 2750–2758 |
| Number of pages | 9 |
| Journal | Crystal Growth and Design |
| Volume | 18 |
| Issue number | 5 |
| Early online date | 26 Mar 2018 |
| DOIs | |
| Publication status | Published - 2 May 2018 |
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Keywords
- ToF SIMS
- single crystal
- paracetamol
- 4-nitrophenol
- chemical characterisation
- morphology
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Impact of paracetamol impurities on face properties : investigating the surface of single crystals using TOF-SIMS. / Ottoboni, Sara; Chrubasik, Michael; Mir Bruce, Layla; Nguyen, Thai Thu Hien; Robertson, Murray; Johnston, Blair; Oswald, Iain D. H.; Florence, Alastair; Price, Chris.
In: Crystal Growth and Design, Vol. 18, No. 5, 02.05.2018, p. 2750–2758.Research output: Contribution to journal › Article
TY - JOUR
T1 - Impact of paracetamol impurities on face 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 - Robertson, Murray
AU - Johnston, Blair
AU - Oswald, Iain D. H.
AU - Florence, Alastair
AU - Price, Chris
PY - 2018/5/2
Y1 - 2018/5/2
N2 - Understanding the mechanism of interaction between pharmaceutical molecules (APIs) and impurities on crystal surfaces is a key concept in understanding purification and for the design of pharmaceutical crystallization processes. Several techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), which provide detailed imaging and elemental surface characterization. Time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identity and distribution. By combining TOF-SIMS, SEM, and optical (OM) and Raman microscopies, we can evaluate the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. 4-Nitrophenol has been selected as an impurity that can be incorporated during crystallization of acetaminophen (paracetamol). This study explores the distribution of impurity and its concentration on the different crystal faces of samples obtained by crystallization over a range of impurity loadings and supersaturation conditions. Raman maps of paracetamol single crystal faces were analyzed using the characteristic Raman peak intensity of 4-nitrophenol to identify regions where it accumulated; Raman maps of three single crystals produced in the presence of 4-nitrophenol using different crystallization procedures highlight how it can be difficult to detect very low concentrations of similar chemical species. In contrast, the 4-nitrophenol monoisotopic mass obtained via TOF-SIMS was shown to be detectable in all the three single crystals produced. This indicates that TOF-SIMS can be a valuable technique for single crystal impurity distribution mapping even when the impurity concentration is very low.
AB - Understanding the mechanism of interaction between pharmaceutical molecules (APIs) and impurities on crystal surfaces is a key concept in understanding purification and for the design of pharmaceutical crystallization processes. Several techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), which provide detailed imaging and elemental surface characterization. Time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identity and distribution. By combining TOF-SIMS, SEM, and optical (OM) and Raman microscopies, we can evaluate the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. 4-Nitrophenol has been selected as an impurity that can be incorporated during crystallization of acetaminophen (paracetamol). This study explores the distribution of impurity and its concentration on the different crystal faces of samples obtained by crystallization over a range of impurity loadings and supersaturation conditions. Raman maps of paracetamol single crystal faces were analyzed using the characteristic Raman peak intensity of 4-nitrophenol to identify regions where it accumulated; Raman maps of three single crystals produced in the presence of 4-nitrophenol using different crystallization procedures highlight how it can be difficult to detect very low concentrations of similar chemical species. In contrast, the 4-nitrophenol monoisotopic mass obtained via TOF-SIMS was shown to be detectable in all the three single crystals produced. This indicates that TOF-SIMS can be a valuable technique for single crystal impurity distribution mapping even when the impurity concentration is very low.
KW - ToF SIMS
KW - single crystal
KW - paracetamol
KW - 4-nitrophenol
KW - chemical characterisation
KW - morphology
UR - https://pubs.acs.org/journal/cgdefu
U2 - 10.1021/acs.cgd.7b01411
DO - 10.1021/acs.cgd.7b01411
M3 - Article
VL - 18
SP - 2750
EP - 2758
JO - Crystal Growth and Design
JF - Crystal Growth and Design
SN - 1528-7483
IS - 5
ER -