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Risk evaluation of impurities in topical excipients: the acetol case

Jente Boonen UGent, Lieselotte Veryser, Lien Taevernier, Nathalie Roche, Kathelijne Peremans UGent, Christian Burvenich UGent and Bart De Spiegeleer UGent (2014) JOURNAL OF PHARMACEUTICAL ANALYSIS.
abstract
Pharmaceutical excipients for topical use may contain impurities, which are often neglected from a toxicity qualification viewpoint. The possible impurities in the most frequently used topical excipients were evaluated in-silico for their toxicity hazard. Acetol, an impurity likely present in different topical pharmaceutical excipients such as propylene glycol and glycerol, was withheld for the evaluation of its health risk after dermal exposure. An ex-vivo in-vitro permeation study using human skin in a Franz Diffusion Cell set-up and GC as quantification methodology showed a significant skin penetration with an overall Kp value of 1.82×10−3 cm/h. Using these data, limit specifications after application of a dermal pharmaceutical product were estimated. Based on the TTC approach of Cramer class I substances, i.e. 1800 µg/(day∙person), the toxicity-qualified specification limits of acetol in topical excipients were calculated to be 90 µg/mL and 180 µg/mL for propylene glycol and glycerol, respectively. It is concluded that setting specification limits for impurities within a quality-by-design approach requires a case-by-case evaluation as demonstrated here with acetol.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
in press
subject
keyword
Transdermal penetration, Specification limits, Excipients, Impurity, Acetol
journal title
JOURNAL OF PHARMACEUTICAL ANALYSIS
J. Pharm. Anal.
ISSN
2095-1779
DOI
10.1016/j.jpha.2013.12.006
language
English
UGent publication?
yes
classification
A2
copyright statement
I have transferred the copyright for this publication to the publisher
id
4427287
handle
http://hdl.handle.net/1854/LU-4427287
date created
2014-06-24 09:25:26
date last changed
2016-12-19 15:43:33
@article{4427287,
  abstract     = {Pharmaceutical excipients for topical use may contain impurities, which are often neglected from a toxicity qualification viewpoint. The possible impurities in the most frequently used topical excipients were evaluated in-silico for their toxicity hazard. Acetol, an impurity likely present in different topical pharmaceutical excipients such as propylene glycol and glycerol, was withheld for the evaluation of its health risk after dermal exposure.
An ex-vivo in-vitro permeation study using human skin in a Franz Diffusion Cell set-up and GC as quantification methodology showed a significant skin penetration with an overall Kp value of 1.82{\texttimes}10\ensuremath{-}3 cm/h. Using these data, limit specifications after application of a dermal pharmaceutical product were estimated. Based on the TTC approach of Cramer class I substances, i.e. 1800 {\textmu}g/(day\unmatched{2219}person), the toxicity-qualified specification limits of acetol in topical excipients were calculated to be 90 {\textmu}g/mL and 180 {\textmu}g/mL for propylene glycol and glycerol, respectively.
It is concluded that setting specification limits for impurities within a quality-by-design approach requires a case-by-case evaluation as demonstrated here with acetol.},
  author       = {Boonen, Jente and Veryser, Lieselotte and Taevernier, Lien and Roche, Nathalie and Peremans, Kathelijne and Burvenich, Christian and De Spiegeleer, Bart},
  issn         = {2095-1779},
  journal      = {JOURNAL OF PHARMACEUTICAL ANALYSIS},
  keyword      = {Transdermal penetration,Specification limits,Excipients,Impurity,Acetol},
  language     = {eng},
  title        = {Risk evaluation of impurities in topical excipients: the acetol case},
  url          = {http://dx.doi.org/10.1016/j.jpha.2013.12.006},
  year         = {2014},
}

Chicago
Boonen, Jente, Lieselotte Veryser, Lien Taevernier, NATHALIE ROCHE, Kathelijne Peremans, Christian Burvenich, and Bart De Spiegeleer. 2014. “Risk Evaluation of Impurities in Topical Excipients: The Acetol Case.” Journal of Pharmaceutical Analysis.
APA
Boonen, Jente, Veryser, L., Taevernier, L., ROCHE, N., Peremans, K., Burvenich, C., & De Spiegeleer, B. (2014). Risk evaluation of impurities in topical excipients: the acetol case. JOURNAL OF PHARMACEUTICAL ANALYSIS.
Vancouver
1.
Boonen J, Veryser L, Taevernier L, ROCHE N, Peremans K, Burvenich C, et al. Risk evaluation of impurities in topical excipients: the acetol case. JOURNAL OF PHARMACEUTICAL ANALYSIS. 2014;
MLA
Boonen, Jente, Lieselotte Veryser, Lien Taevernier, et al. “Risk Evaluation of Impurities in Topical Excipients: The Acetol Case.” JOURNAL OF PHARMACEUTICAL ANALYSIS (2014): n. pag. Print.