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Risk evaluation of impurities in topical excipients: the acetol case

Jente Boonen (UGent) , Lieselotte Veryser (UGent) , Lien Taevernier (UGent) , Nathalie Roche (UGent) , Kathelijne Peremans (UGent) , Christian Burvenich (UGent) and Bart De Spiegeleer (UGent)
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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.
Keywords
Transdermal penetration, Specification limits, Excipients, Impurity, Acetol

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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.
@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},
}

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