Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers
Exposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/9/899 |
| _version_ | 1797552990551277568 |
|---|---|
| author | Agata Kryczyk-Poprawa István Zupkó Péter Bérdi Paweł Żmudzki Justyna Popiół Bożena Muszyńska Włodzimierz Opoka |
| author_facet | Agata Kryczyk-Poprawa István Zupkó Péter Bérdi Paweł Żmudzki Justyna Popiół Bożena Muszyńska Włodzimierz Opoka |
| author_sort | Agata Kryczyk-Poprawa |
| collection | DOAJ |
| description | Exposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an in-depth analysis of the photostability of tazarotene in ethanolic solution in the presence of zinc oxide and/or titanium dioxide as well as benzophenone-type UV filters was performed. Eleven presumed products were derived from the photocatalytic degradation of tazarotene using ultra-performance liquid chromatography–tandem mass spectrometry, and transformation pathways were proposed. The degradation process mainly affected the 4,4-dimethyl-3,4-dihydro-2<i>H</i>-thiopyran moiety. The fragments most susceptible to oxidation were the methyl groups and the sulfur atom. Moreover, in the presence of sulisobenzone, under UV irradiation, tazarotene was subjected to a degradation process, which resulted in two photodecomposition products. <i>In silico</i> studies performed by OSIRIS Property Explorer demonstrated that five of the degradation products could be harmful in terms of the reproductive effects, which are associated with 3,4-dihydro-6-methyl-2<i>H</i>-1-benzothiopyran 1,1-dioxide, while one of them demonstrated potential irritant activity. The cytotoxic properties of the degradation products of tazarotene were assessed by MTT assay on a panel of human adherent cancer cells. Time- and concentration-dependent growth inhibition was evidenced in ovary (A2780) and breast (MDA-MB-231) cancer cell lines. The potential implication of the outcomes of the present research requires further studies mainly concerning the photostability of tazarotene in the topical formulations. |
| first_indexed | 2024-03-10T16:09:03Z |
| format | Article |
| id | doaj.art-c550c185d05448d984ece7edf2aaf9fc |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T16:09:03Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c550c185d05448d984ece7edf2aaf9fc2023-11-20T14:37:41ZengMDPI AGPharmaceutics1999-49232020-09-0112989910.3390/pharmaceutics12090899Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV AbsorbersAgata Kryczyk-Poprawa0István Zupkó1Péter Bérdi2Paweł Żmudzki3Justyna Popiół4Bożena Muszyńska5Włodzimierz Opoka6Department of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, 6720 Szeged, HungaryDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, 6720 Szeged, HungaryDepartment of Medicinal Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandDepartment of Pharmaceutical Biochemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandDepartment of Pharmaceutical Botany, Jagiellonian University Collegium Medicum, 30-688 Kraków, PolandDepartment of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandExposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an in-depth analysis of the photostability of tazarotene in ethanolic solution in the presence of zinc oxide and/or titanium dioxide as well as benzophenone-type UV filters was performed. Eleven presumed products were derived from the photocatalytic degradation of tazarotene using ultra-performance liquid chromatography–tandem mass spectrometry, and transformation pathways were proposed. The degradation process mainly affected the 4,4-dimethyl-3,4-dihydro-2<i>H</i>-thiopyran moiety. The fragments most susceptible to oxidation were the methyl groups and the sulfur atom. Moreover, in the presence of sulisobenzone, under UV irradiation, tazarotene was subjected to a degradation process, which resulted in two photodecomposition products. <i>In silico</i> studies performed by OSIRIS Property Explorer demonstrated that five of the degradation products could be harmful in terms of the reproductive effects, which are associated with 3,4-dihydro-6-methyl-2<i>H</i>-1-benzothiopyran 1,1-dioxide, while one of them demonstrated potential irritant activity. The cytotoxic properties of the degradation products of tazarotene were assessed by MTT assay on a panel of human adherent cancer cells. Time- and concentration-dependent growth inhibition was evidenced in ovary (A2780) and breast (MDA-MB-231) cancer cell lines. The potential implication of the outcomes of the present research requires further studies mainly concerning the photostability of tazarotene in the topical formulations.https://www.mdpi.com/1999-4923/12/9/899tazarotenephotostability studiesphotocatalytic degradationbenzophenonesTiO<sub>2</sub>ZnO |
| spellingShingle | Agata Kryczyk-Poprawa István Zupkó Péter Bérdi Paweł Żmudzki Justyna Popiół Bożena Muszyńska Włodzimierz Opoka Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers Pharmaceutics tazarotene photostability studies photocatalytic degradation benzophenones TiO<sub>2</sub> ZnO |
| title | Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers |
| title_full | Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers |
| title_fullStr | Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers |
| title_full_unstemmed | Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers |
| title_short | Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers |
| title_sort | photostability testing of a third generation retinoid tazarotene in the presence of uv absorbers |
| topic | tazarotene photostability studies photocatalytic degradation benzophenones TiO<sub>2</sub> ZnO |
| url | https://www.mdpi.com/1999-4923/12/9/899 |
| work_keys_str_mv | AT agatakryczykpoprawa photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers AT istvanzupko photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers AT peterberdi photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers AT pawełzmudzki photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers AT justynapopioł photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers AT bozenamuszynska photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers AT włodzimierzopoka photostabilitytestingofathirdgenerationretinoidtazaroteneinthepresenceofuvabsorbers |