Risk evaluation of impurities in topical excipients: The acetol case
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 differ...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-10-01
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| Series: | Journal of Pharmaceutical Analysis |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177913001512 |
| _version_ | 1818448093460299776 |
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| author | Jente Boonen Lieselotte Veryser Lien Taevernier Nathalie Roche Kathelijne Peremans Christian Burvenich Bart De Spiegeleer |
| author_facet | Jente Boonen Lieselotte Veryser Lien Taevernier Nathalie Roche Kathelijne Peremans Christian Burvenich Bart De Spiegeleer |
| author_sort | Jente Boonen |
| collection | DOAJ |
| description | 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 1.82Ã10â3 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/(dayâperson), 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: Acetol, Impurity, Excipients, Transdermal penetration, Specification limits |
| first_indexed | 2024-12-14T20:14:02Z |
| format | Article |
| id | doaj.art-1fe9c28de2e0422aa61709b818be0cec |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-14T20:14:02Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-1fe9c28de2e0422aa61709b818be0cec2022-12-21T22:48:53ZengElsevierJournal of Pharmaceutical Analysis2095-17792014-10-0145303315Risk evaluation of impurities in topical excipients: The acetol caseJente Boonen0Lieselotte Veryser1Lien Taevernier2Nathalie Roche3Kathelijne Peremans4Christian Burvenich5Bart De Spiegeleer6Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, BelgiumDrug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, BelgiumDrug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, BelgiumDepartment of Plastic and Reconstructive Surgery, University Hospital Ghent, De Pintelaan 185, B-9000 Ghent, BelgiumDepartment of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, BelgiumDepartment of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, BelgiumDrug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium; Corresponding author. Tel.: +32 9 264 81 00; fax: +32 9 264 81 93.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 1.82Ã10â3 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/(dayâperson), 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: Acetol, Impurity, Excipients, Transdermal penetration, Specification limitshttp://www.sciencedirect.com/science/article/pii/S2095177913001512 |
| spellingShingle | Jente Boonen Lieselotte Veryser Lien Taevernier Nathalie Roche Kathelijne Peremans Christian Burvenich Bart De Spiegeleer Risk evaluation of impurities in topical excipients: The acetol case Journal of Pharmaceutical Analysis |
| title | Risk evaluation of impurities in topical excipients: The acetol case |
| title_full | Risk evaluation of impurities in topical excipients: The acetol case |
| title_fullStr | Risk evaluation of impurities in topical excipients: The acetol case |
| title_full_unstemmed | Risk evaluation of impurities in topical excipients: The acetol case |
| title_short | Risk evaluation of impurities in topical excipients: The acetol case |
| title_sort | risk evaluation of impurities in topical excipients the acetol case |
| url | http://www.sciencedirect.com/science/article/pii/S2095177913001512 |
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