title: Development of transdermal therapeutic formulation of CNS5161, a novel N-methyl-D-aspartate receptor antagonist, by utilizing pressure-sensitive adhesives I.
abstract: The aim of this study was to investigate the feasibility of percutaneous absorption of CNS5161, a novel N-methyl-D-aspartate (NMDA) receptor antagonist developed as a potential treatment for neuropathic pain and other neurological disorders. Six pressure-sensitive adhesives (PSA) with different physicochemical properties, namely, styrene-isoprene-styrene (1) (SIS(1)), styrene-isoprene-styrene (2) (SIS(2)), silicone, acrylate with a hydroxyl group (acrylate(OH)), acrylate without a functional group (acrylate(none)) and acrylate with a carboxyl group (acrylate(COOH)), were investigated for their release of CNS5161 and its subsequent skin permeability. Among the adhesives examined, silicone PSA provided the highest value of transdermal flux of CNS5161, which could be attributable to the highest release rate from it due to its very high thermodynamic activity. Although CNS5161 was also in the supersaturated state in SIS(1) and SIS(2) PSAs, the release and transdermal permeation from these adhesives were slower than those from silicone PSA. As for the acrylic PSAs, the highest release rate and permeability of CNS5161 were observed for acrylate(OH) PSA, followed by acrylate(none) and acrylate(COOH) PSAs, but none of them was better in terms of either the release or the permeability of CNS5161 than silicone PSA. These results clearly indicated that silicone PSA would be the most suitable for transdermal delivery of CNS5161 and silicone PSA containing 10% CNS5161 would be suitable for clinical use in humans.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Naruse
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogawara
authors.forename: Toshikiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Ryoji
authors.initials: R
authors.lastname: Konishi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
mesh_terms: D000279:Administration, Cutaneous; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D016503:Drug Delivery Systems; D006146:Guanidines / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012828:Silicones / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D014014:Tissue Adhesives / Q000737:chemistry*
chemical_list: D000700:Analgesics; C468267:CNS 5161; D006146:Guanidines; D016194:Receptors, N-Methyl-D-Aspartate; D012828:Silicones; D013438:Sulfhydryl Compounds; D014014:Tissue Adhesives