title: Corticosteroid solubility and lipid polarity control release from solid lipid nanoparticles.
abstract: Solid lipid nanoparticles (SLN) show promise as a drug delivery system for skin administration. The solid state of the lipid particle enables efficient drug encapsulation and controlled drug release. The present study addresses the influence of lipid composition and drug substance lipid solubility on the in vitro release profile of corticosteroids from SLN for topical administration. Firstly, the effect of lipid composition on the lipid solubility and in vitro release of betamethasone-17-valerate (BMV) was determined by varying the lipid monoglyceride content and the chain length of the fatty acid moiety. Secondly, the effect of drug substance physicochemical properties was determined by studying five different corticosteroid derivatives with different lipophilicity. A high concentration of monoglyceride in SLN increased the amount of BMV released. The corticosteroid release rate depended on the drug substance lipophilicity and it was clear that the release profiles depended on drug partitioning to the aqueous phase as indicated by zero order kinetics. The results emphasize that the corticosteroid solubility in the lipid phase greatly influence drug distribution in the lipid particles and release properties. Thus knowledge of drug substance solubility and lipid polarity contributes to optimize SLN release properties.
authors.affiliation: LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark. louise.bastholm-jensen@leo-pharma.com
authors.forename: Louise B
authors.initials: LB
authors.lastname: Jensen
authors.forename: Emily
authors.initials: E
authors.lastname: Magnussson
authors.forename: Linda
authors.initials: L
authors.lastname: Gunnarsson
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vermehren
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Nielsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Petersson
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004075:Diglycerides / Q000737:chemistry; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010168:Palmitates / Q000737:chemistry; D010316:Particle Size; D012995:Solubility; D014280:Triglycerides / Q000737:chemistry; D014783:Viscosity
chemical_list: D000305:Adrenal Cortex Hormones; D003692:Delayed-Action Preparations; D004075:Diglycerides; D008055:Lipids; D010168:Palmitates; D014280:Triglycerides; C007975:hydrocortisone-17-butyrate; C021650:hydrocortisone acetate; C006957:cetyl palmitate; D001624:Betamethasone Valerate; D006854:Hydrocortisone