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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...

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Autores principales: 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.
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
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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.
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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
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