Cargando…
Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains
Raynaud’s Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatm...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920966/ https://www.ncbi.nlm.nih.gov/pubmed/31717566 http://dx.doi.org/10.3390/pharmaceutics11110594 |
_version_ | 1783481054771806208 |
---|---|
author | Wasan, Ellen K. Zhao, Jinying Poteet, Joshua Mohammed, Munawar A. Syeda, Jaweria Orlowski, Tatiana Soulsbury, Kevin Cawthray, Jacqueline Bunyamin, Amanda Zhang, Chi Fahlman, Brian M. Krol, Ed S. |
author_facet | Wasan, Ellen K. Zhao, Jinying Poteet, Joshua Mohammed, Munawar A. Syeda, Jaweria Orlowski, Tatiana Soulsbury, Kevin Cawthray, Jacqueline Bunyamin, Amanda Zhang, Chi Fahlman, Brian M. Krol, Ed S. |
author_sort | Wasan, Ellen K. |
collection | PubMed |
description | Raynaud’s Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatment to reduce the incidence and severity of attacks when other interventions fail to alleviate the condition and there is danger of tissue injury. Oral administration of nifedipine, however, is associated with systemic adverse effects, and thus topical administration with nifedipine locally to the extremities would be advantageous. However, nifedipine is subject to rapid photodegradation, which is problematic for exposed skin such as the hands. The goal of this project was to analyze the photostability of a novel topical nifedipine cream to UVA light. The effect of incorporating the photoprotectants rutin, quercetin, and/or avobenzone (BMDBM) into the nifedipine cream on the stability of nifedipine to UVA light exposure and the appearance of degradation products of nifedipine was determined. Rutin and quercetin are flavonoids with antioxidant activity. Both have the potential to improve the photostability of nifedipine by a number of mechanisms that either quench the intermolecular electron transfer of the singlet excited dihydropyridine to the nitrobenzene group or by preventing photoexcitation of nifedipine. Rutin at either 0.1% or 0.5% (w/w) did not improve the stability of nifedipine 2% (w/w) in the cream after UVA exposure up to 3 h. Incorporation of quercetin at 0.5% (w/w) did improve nifedipine stability from 40% (no quercetin) to 77% (with quercetin) of original drug concentration after 3 h UVA exposure. A combination of BMDBM and quercetin was the most effective photoprotectant for maintaining nifedipine concentration following up to 8 h UVA exposure. |
format | Online Article Text |
id | pubmed-6920966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69209662019-12-24 Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains Wasan, Ellen K. Zhao, Jinying Poteet, Joshua Mohammed, Munawar A. Syeda, Jaweria Orlowski, Tatiana Soulsbury, Kevin Cawthray, Jacqueline Bunyamin, Amanda Zhang, Chi Fahlman, Brian M. Krol, Ed S. Pharmaceutics Article Raynaud’s Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatment to reduce the incidence and severity of attacks when other interventions fail to alleviate the condition and there is danger of tissue injury. Oral administration of nifedipine, however, is associated with systemic adverse effects, and thus topical administration with nifedipine locally to the extremities would be advantageous. However, nifedipine is subject to rapid photodegradation, which is problematic for exposed skin such as the hands. The goal of this project was to analyze the photostability of a novel topical nifedipine cream to UVA light. The effect of incorporating the photoprotectants rutin, quercetin, and/or avobenzone (BMDBM) into the nifedipine cream on the stability of nifedipine to UVA light exposure and the appearance of degradation products of nifedipine was determined. Rutin and quercetin are flavonoids with antioxidant activity. Both have the potential to improve the photostability of nifedipine by a number of mechanisms that either quench the intermolecular electron transfer of the singlet excited dihydropyridine to the nitrobenzene group or by preventing photoexcitation of nifedipine. Rutin at either 0.1% or 0.5% (w/w) did not improve the stability of nifedipine 2% (w/w) in the cream after UVA exposure up to 3 h. Incorporation of quercetin at 0.5% (w/w) did improve nifedipine stability from 40% (no quercetin) to 77% (with quercetin) of original drug concentration after 3 h UVA exposure. A combination of BMDBM and quercetin was the most effective photoprotectant for maintaining nifedipine concentration following up to 8 h UVA exposure. MDPI 2019-11-09 /pmc/articles/PMC6920966/ /pubmed/31717566 http://dx.doi.org/10.3390/pharmaceutics11110594 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wasan, Ellen K. Zhao, Jinying Poteet, Joshua Mohammed, Munawar A. Syeda, Jaweria Orlowski, Tatiana Soulsbury, Kevin Cawthray, Jacqueline Bunyamin, Amanda Zhang, Chi Fahlman, Brian M. Krol, Ed S. Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains |
title | Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains |
title_full | Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains |
title_fullStr | Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains |
title_full_unstemmed | Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains |
title_short | Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains |
title_sort | development of a uv-stabilized topical formulation of nifedipine for the treatment of raynaud phenomenon and chilblains |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920966/ https://www.ncbi.nlm.nih.gov/pubmed/31717566 http://dx.doi.org/10.3390/pharmaceutics11110594 |
work_keys_str_mv | AT wasanellenk developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT zhaojinying developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT poteetjoshua developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT mohammedmunawara developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT syedajaweria developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT orlowskitatiana developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT soulsburykevin developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT cawthrayjacqueline developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT bunyaminamanda developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT zhangchi developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT fahlmanbrianm developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains AT kroleds developmentofauvstabilizedtopicalformulationofnifedipineforthetreatmentofraynaudphenomenonandchilblains |