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Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate
Repeated oral administration of mexazolam, an anti-anxiety agent, may cause adverse effects such as gastric disturbance, drowsiness, and ataxia due to transiently high blood levels. Transdermal administration would avoid the systemic side effects and gastric disorders after oral administration. We h...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shaheed Beheshti University of Medical Sciences
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876569/ https://www.ncbi.nlm.nih.gov/pubmed/25317180 |
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author | Weon Cho, Cheong Chul Shin, Sang |
author_facet | Weon Cho, Cheong Chul Shin, Sang |
author_sort | Weon Cho, Cheong |
collection | PubMed |
description | Repeated oral administration of mexazolam, an anti-anxiety agent, may cause adverse effects such as gastric disturbance, drowsiness, and ataxia due to transiently high blood levels. Transdermal administration would avoid the systemic side effects and gastric disorders after oral administration. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of mexazolam. Drug solubility was highest at 40% PEG-400 volume fraction. The release and permeation profiles through the rat skin were determined for 24 h using a modified Keshary-Chien diffusion cell. The drug release was increased by increasing the concentration with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy (E(a)), which was measured from a slope of log P versus 1000/T plot, was 8.64 Kcal/mol for a 1.5% loading dose. To reduce the brittleness and increase the pore of the EVA matrix, diffrent plasticizers were used. Among the plasticizers, including the citrates or the phthalate groups, diethyl phthalate showed the highest effect on the release of mexazolam. To increase the skin permeation of mexazolam from the EVA matrix, enhancers such as the fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were added to the EVA matrix, respectively, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Among the several enhancers used, N-methyl-2-pyrrolidone showed the best enhancement factor. In conclusion, enhanced transdermal delivery of mexazolam through an EVA matrix containing plasticizer and a permeation enhancer could be useful in the development of a transdermal drug delivery system. |
format | Online Article Text |
id | pubmed-3876569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Shaheed Beheshti University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-38765692014-10-14 Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate Weon Cho, Cheong Chul Shin, Sang Iran J Pharm Res Original Article Repeated oral administration of mexazolam, an anti-anxiety agent, may cause adverse effects such as gastric disturbance, drowsiness, and ataxia due to transiently high blood levels. Transdermal administration would avoid the systemic side effects and gastric disorders after oral administration. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of mexazolam. Drug solubility was highest at 40% PEG-400 volume fraction. The release and permeation profiles through the rat skin were determined for 24 h using a modified Keshary-Chien diffusion cell. The drug release was increased by increasing the concentration with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy (E(a)), which was measured from a slope of log P versus 1000/T plot, was 8.64 Kcal/mol for a 1.5% loading dose. To reduce the brittleness and increase the pore of the EVA matrix, diffrent plasticizers were used. Among the plasticizers, including the citrates or the phthalate groups, diethyl phthalate showed the highest effect on the release of mexazolam. To increase the skin permeation of mexazolam from the EVA matrix, enhancers such as the fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were added to the EVA matrix, respectively, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Among the several enhancers used, N-methyl-2-pyrrolidone showed the best enhancement factor. In conclusion, enhanced transdermal delivery of mexazolam through an EVA matrix containing plasticizer and a permeation enhancer could be useful in the development of a transdermal drug delivery system. Shaheed Beheshti University of Medical Sciences 2012 /pmc/articles/PMC3876569/ /pubmed/25317180 Text en © 2012 by School of Pharmacy, Shaheed Beheshti University of Medical Sciences and Health Services This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Weon Cho, Cheong Chul Shin, Sang Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate |
title | Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate |
title_full | Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate |
title_fullStr | Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate |
title_full_unstemmed | Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate |
title_short | Enhanced Controlled Transdermal Delivery of Mexazolam Using Ethylene-vinyl Acetate |
title_sort | enhanced controlled transdermal delivery of mexazolam using ethylene-vinyl acetate |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876569/ https://www.ncbi.nlm.nih.gov/pubmed/25317180 |
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