PMID- 17884312
OWN - NLM
STAT- MEDLINE
DCOM- 20080311
LR  - 20161124
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 349
IP  - 1-2
DP  - 2008 Feb 12
TI  - The impact of low-level inorganic impurities on key physicochemical properties of 
      paracetamol.
PG  - 61-5
AB  - Trace inorganic impurities in active pharmaceutical ingredients (APIs) while 
      having limited toxicological significance might affect the down stream processing 
      properties of those substances. The level of impurities in paracetamol batches 
      was quantified and mapped using inductively coupled polarization mass 
      spectrometry (ICP-MS) and scanning electron microscopy coupled with energy 
      dispersive X-ray microanalysis (SEM-EDX). The physical form of samples was 
      assessed using X-ray powder diffraction (XRPD) and characterised thermally using 
      differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). 
      Surface properties were evaluated using inverse gas chromatography (IGC) and 
      moisture sorption. Size distribution was measured using an aerosizer with dry 
      powder dispersion. Physical analysis confirmed that the batches were of the same 
      physical form and particle size distribution was shown to be similar. The SEM-EDX 
      analysis however revealed the presence of aluminium on the surface of particles. 
      This was supported by ICP-MS analysis, which showed different levels of aluminium 
      between batches ranging from 0.1 to 5.6 ppm. IGC indicated that the batches with 
      the highest aluminium content had the highest dispersive free energy. Differences 
      in levels of inorganic impurities typically not considered significant in drug 
      substance specifications correspond with differences in physical properties of 
      APIs, with potential downstream consequences for processing and finished product 
      performance.
FAU - Hulse, Wendy L
AU  - Hulse WL
AD  - Institute of Pharmaceutical Innovation, University of Bradford, Bradford, UK. 
      wendy.3.hulse@GSK.com
FAU - Grimsey, Ian M
AU  - Grimsey IM
FAU - De Matas, Marcel
AU  - De Matas M
LA  - eng
PT  - Journal Article
DEP - 20070806
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 362O9ITL9D (Acetaminophen)
SB  - IM
MH  - Absorption
MH  - Acetaminophen/*chemistry
MH  - Analgesics, Non-Narcotic/*chemistry
MH  - Calorimetry, Differential Scanning
MH  - Chemical Phenomena
MH  - Chemistry, Physical
MH  - Chromatography, Gas
MH  - Drug Contamination
MH  - Electron Probe Microanalysis
MH  - Humidity
MH  - Mass Spectrometry
MH  - Microscopy, Electron, Scanning
MH  - Particle Size
MH  - Temperature
EDAT- 2007/09/22 09:00
MHDA- 2008/03/12 09:00
CRDT- 2007/09/22 09:00
PHST- 2007/02/05 00:00 [received]
PHST- 2007/07/15 00:00 [revised]
PHST- 2007/07/20 00:00 [accepted]
PHST- 2007/09/22 09:00 [pubmed]
PHST- 2008/03/12 09:00 [medline]
PHST- 2007/09/22 09:00 [entrez]
AID - S0378-5173(07)00639-4 [pii]
AID - 10.1016/j.ijpharm.2007.07.037 [doi]
PST - ppublish
SO  - Int J Pharm. 2008 Feb 12;349(1-2):61-5. doi: 10.1016/j.ijpharm.2007.07.037. Epub 
      2007 Aug 6.