title: Development of a new formulation combining calcipotriol and betamethasone dipropionate in an ointment vehicle.
abstract: Calcipotriol and betamethasone dipropionate are widely used effective treatments for psoriasis. Combined therapy is known to be superior to monotherapy, but current formulations do not permit simultaneous application as the drug substances will degrade when mixed. The purpose of the study was to develop a formulation which combines calcipotriol and betamethasone dipropionate in a single vehicle hereby achieving optimal delivery of both substances into the skin. As the two substances are incompatible in aqueous and alcoholic medias, different non-aqueous formulations were prepared. Skin permeation studies were investigated using Franz-type diffusion cells. Formulations based on isopropyl myristate were found to decrease the permeation rate (25-35%) as compared with marketed monotherapy products (set to 100%). Lanolin had no overall effect on skin permeability. However, polyoxypropylene-15 stearyl ether (PSE) had a marked effect. A 5% PSE formulation resulted in a permeation rate comparable to the marketed products. Thus, by using PSE as solvent, it was possible to combine calcipotriol and betamethasone dipropionate in a single formulation while optimal skin permeability was attained. Recently, the efficiency of this formulation (Daivobet) has been verified in clinical studies showing an improved efficacy in the treatment of psoriatic patients.
authors.affiliation: Pharmaceutical Development, LEO Pharma, Ballerup, Denmark. lene.simonsen@leo-pharma.com
authors.forename: Lene
authors.initials: L
authors.lastname: Simonsen
authors.forename: Gert
authors.initials: G
authors.lastname: Høy
authors.forename: Erik
authors.initials: E
authors.lastname: Didriksen
authors.forename: Jette
authors.initials: J
authors.lastname: Persson
authors.forename: Nina
authors.initials: N
authors.lastname: Melchior
authors.forename: Jens
authors.initials: J
authors.lastname: Hansen
mesh_terms: D000287:Administration, Topical; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000737:chemistry*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003718:Denmark; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods*; D015195:Drug Design; D006801:Humans; D009824:Ointments / Q000737:chemistry* / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000737:chemistry* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012995:Solubility / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D009824:Ointments; D014677:Pharmaceutical Vehicles; C055085:calcipotriene; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D002117:Calcitriol