title: A prodrug approach to enhance azelaic acid percutaneous availability.
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.
authors.affiliation: a Department of Pharmaceutical Sciences, Faculty of Pharmacy , The University of Jordan , Amman , Jordan.
authors.forename: Sara
authors.initials: S
authors.lastname: Al-Marabeh
authors.affiliation: b Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy , The University of Jordan , Amman , Jordan.
authors.forename: Enam
authors.initials: E
authors.lastname: Khalil
authors.affiliation: a Department of Pharmaceutical Sciences, Faculty of Pharmacy , The University of Jordan , Amman , Jordan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khanfar
authors.affiliation: b Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy , The University of Jordan , Amman , Jordan.
authors.forename: Amal G
authors.initials: AG
authors.lastname: Al-Bakri
authors.affiliation: a Department of Pharmaceutical Sciences, Faculty of Pharmacy , The University of Jordan , Amman , Jordan.|c Faculty of Pharmacy , Al-Zaytoonah Private University of Jordan , Amman , Jordan.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Alzweiri
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy; D000279:Administration, Cutaneous; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011425:Propionibacterium acnes / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D003879:Dermatologic Agents; D003998:Dicarboxylic Acids; D011355:Prodrugs; C062819:diethyl azelate; C010038:azelaic acid
keywords: Azelaic acid; diffusion and stratum corneum; prodrug