title: Efficient ibuprofen delivery from anhydrous semisolid formulation based on a novel cross-linked silicone polymer network: an in vitro and in vivo study.
abstract: The use of silicone as a primary polymer in topical semisolid pharmaceutical formulations is infrequent. Recent development of novel silicone materials provides an opportunity to investigate their drug delivery efficiencies. In this study, an anhydrous semisolid formulation was prepared using a novel cross-linked silicone polymer network swollen in isododecane. Similar formulations were prepared using petrolatum, an acrylic, or a cellulose polymer. All formulations contained 5% ibuprofen (IBP). In vitro permeability was evaluated for all formulations and a commercial product using human cadaver epidermis. The silicone formulation delivered IBP more efficiently than all other formulations in terms of flux, cumulative amount, and percent drug release. The silicone formulation showed the maximum flux of 85.9 μg . cm(-2) . h(-1) and a cumulative IBP release of 261.6 μg in 8 h, whereas the benchmark showed 20.1 μg . cm(-2) . h(-1) and 30.9 μg, respectively. An in vivo study conducted on rats showed calculated blood AUCs of 59.2 and 17.6 μg . h/g (p < 0.003) for the silicone formulation and the benchmark, respectively. The IBP in excised rat skin was 264 ± 59 μg/g for the silicone formulation and 102 ± 5 μg/g for the benchmark. The results obtained from the in vitro and in vivo studies demonstrate efficient topical IBP delivery by the silicone formulation.
authors.affiliation: Dow Corning Corporation, Healthcare Industry, Pharmaceutics, Midland, Michigan 48686. Electronic address: hyder.aliyar@dowcorning.com.
authors.forename: Hyder
authors.initials: H
authors.lastname: Aliyar
authors.affiliation: Dow Corning Corporation, Healthcare Industry, Pharmaceutics, Midland, Michigan 48686.
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.affiliation: Dow Corning Corporation, Healthcare Industry, Pharmaceutics, Midland, Michigan 48686.
authors.forename: Gary
authors.initials: G
authors.lastname: Loubert
authors.affiliation: Dow Corning Corporation, Healthcare Industry, Pharmaceutics, Midland, Michigan 48686.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schalau
mesh_terms: D000279:Administration, Cutaneous; D000812:Anhydrides / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002102:Cadaver; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D017646:Organosilicon Compounds / Q000737:chemistry*; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D011916:Rats, Inbred F344; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014018:Tissue Distribution
chemical_list: D000812:Anhydrides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D017646:Organosilicon Compounds; D011108:Polymers; D007052:Ibuprofen
keywords: drug excipient interactions; excipients; formulation; gels; permeability; polymeric drug delivery systems; semi-solids; skin; transdermal drug delivery