A prodrug approach to enhance azelaic acid percutaneous availability. (19th May 2017)

• Record Type: Journal Article
• Authors: Al-Marabeh, Sara; Khalil, Enam; Khanfar, Mohammad; Al-Bakri, Amal G.; Alzweiri, Muhammed
• Is Part Of: Pharmaceutical development and technology. Volume 22:Number 4(2017)
• Page Start: 578
• Page End: 586
• Publication Date: 2017-05-19
• Subjects: Azelaic acid -- diffusion and stratum corneum -- prodrug; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.1080/10837450.2016.1200614
• Languages: English
• ISSNs: 1083-7450

Abstract

Abstract: Azelaic acid is a dicarboxylic acid compound used in treatment of acne vulgaris. However, high concentration ( ca 20%) is needed to guarantee the drug availability in the skin. The latter increases the incidence of side effects such as local irritation. The prodrug strategy to enhance azelaic acid diffusion through skin was not reported before. Thus, a lipophilic prodrug of azelaic acid (diethyl azelate [DEA]) was synthesized and investigated to improve percutaneous availability of azelaic acid, with a subsequent full physical, chemical, and biological characterization. Expectedly, DEA exhibited a significant increase in diffusion compared to azelaic acid through silicone membrane. In contrast, the diffusion results through human stratum corneum (SC) displayed weaker permeation for DEA with expected retention in the SC. Therefore, a desorption study of DEA from SC was conducted to examine the reservoir behavior in SC. Results showed an evidence of sustained release behavior of DEA from SC. Consequently, enhancement of keratolytic effect is expected due to azelaic acid produced from enzymatic conversion of DEA released from SC.