title: Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate.
abstract: Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 µm in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 µm) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 µm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs.
authors.affiliation: a Department of Biopharmaceutics , Kyoto Pharmaceutical University , Kyoto , Japan ;
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: a Department of Biopharmaceutics , Kyoto Pharmaceutical University , Kyoto , Japan ;
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.affiliation: a Department of Biopharmaceutics , Kyoto Pharmaceutical University , Kyoto , Japan ;|b CosMED Pharmaceutical Co., Ltd. , Kyoto , Japan.
authors.forename: Ying-Shu
authors.initials: YS
authors.lastname: Quan
authors.affiliation: b CosMED Pharmaceutical Co., Ltd. , Kyoto , Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.affiliation: a Department of Biopharmaceutics , Kyoto Pharmaceutical University , Kyoto , Japan ;
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.affiliation: a Department of Biopharmaceutics , Kyoto Pharmaceutical University , Kyoto , Japan ;
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.affiliation: a Department of Biopharmaceutics , Kyoto Pharmaceutical University , Kyoto , Japan ;
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D009339:Needles; D010539:Permeability; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D023422:Skin Irritancy Tests; D012995:Solubility; D018170:Sumatriptan / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D018170:Sumatriptan; D006820:Hyaluronic Acid
keywords: Human skin permeation; microneedle arrays; skin irritation; sodium hyaluronate; sumatriptan succinate; transdermal drug delivery