title: Formulation considerations in the design of topical, polymeric film-forming systems for sustained drug delivery to the skin.
abstract: Polymeric film-forming systems (FFSs) are potential drug delivery systems for topical application to the skin. The FFSs form thin and transparent polymeric films in situ upon solvent evaporation. Their application convenience and cosmetic attributes, superior to conventional semi-solids, may offer improved patient compliance. This study represents the first phase of an investigation into the use of FFSs for prolonged dermal drug delivery. FFS formulations were distinguished based on their ability to sustain the release of betamethasone 17-valerate (BMV) in vitro over 72 h. The effect of film-forming polymer (hydrophilic: hydroxypropyl cellulose (Klucel™ LF); hydrophobic: polymethacrylate copolymers (Eudragit® NE and Eudragit® RS), and polyacrylate copolymer (Dermacryl® 79) was first determined, and then the impact of incorporation of plasticisers (triethyl citrate, tributyl citrate, and dibutyl sebacate) was examined. The Klucel film released a significantly higher amount of BMV than the hydrophobic FFS, 42 versus 4 μg/cm(2), respectively. The release was increased when a plasticiser was incorporated, and with higher enhancement ratios achieved with the more lipophilic plasticisers. In conclusion, the results show that FFSs can sustain drug release (hence representing useful systems for prolonged dermal therapy) and emphasise the importance of the formulation on drug delivery, with the type of polymer being of greatest significance.
authors.affiliation: LEO Pharma A/S, Ballerup, Denmark; University of Bath, Department of Pharmacy & Pharmacology, Bath, UK.
authors.forename: Kit
authors.initials: K
authors.lastname: Frederiksen
authors.affiliation: University of Bath, Department of Pharmacy & Pharmacology, Bath, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
authors.affiliation: LEO Pharma A/S, Ballerup, Denmark. Electronic address: karsten.petersson@leo-pharma.com.
authors.forename: Karsten
authors.initials: K
authors.lastname: Petersson
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D004058:Diffusion; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005938:Glucocorticoids / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D055595:Mechanical Phenomena; D008567:Membranes, Artificial; D010592:Pharmaceutic Aids / Q000737:chemistry*; D010968:Plasticizers / Q000737:chemistry*; D058105:Polymerization; D011109:Polymethacrylic Acids / Q000737:chemistry; D012867:Skin / Q000737:chemistry; D034421:Sus scrofa
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D003879:Dermatologic Agents; C496967:Eudragit NE40D; D005938:Glucocorticoids; D008567:Membranes, Artificial; D010592:Pharmaceutic Aids; D010968:Plasticizers; D011109:Polymethacrylic Acids; C050528:Eudragit RS; D002482:Cellulose; D001624:Betamethasone Valerate; C008079:hydroxypropylcellulose
keywords: Betamethasone 17-valerate; Dermal drug delivery; In vitro release; Plasticiser; Polymeric film-forming systems; Sustained release