title: In vitro release studies of insulin from lipid implants in solution and in a hydrogel matrix mimicking the subcutis.
abstract: Widely accepted in vitro methodologies for sustained release parenteral drug formulations remain to be established. Hydrogels have been proposed as a release matrix more closely resembling the in vivo conditions for formulations intended for subcutaneous administration. The perspective of the current work was to investigate the feasibility of developing UV imaging-based in vitro methods enabling visualization and characterization of drug release and transport of protein therapeutics intended for subcutaneous administration. Specifically, the objectives were to prepare lipid implants providing sustained release of the model protein insulin and investigate the release into 0.5% (w/v) agarose hydrogels, pH7.40, using UV imaging- and a gel sampling-based release testing method. These results were compared to insulin release into well agitated buffer solution. Irrespective of the applied in vitro release method, the insulin release from Sterotex implants with a drug load of 20% (w/w) was faster as compared to the release from implants with a load of 10% (w/w), most likely due to the higher porosity of the implants with increasing drug load. Insulin release from 10% (w/w) implants into agitated solution was faster as compared to release into agarose hydrogel. This was ascribed to the additional mass transfer resistance provided by the agarose hydrogel. Interestingly, the release profiles of insulin from implants with an initial drug load of 20% (w/w) obtained by the three in vitro methods were relatively similar. The gel-based methods, in particular UV imaging, enable monitoring local drug concentrations in the vicinity of the implant over time thereby facilitating assessment of, e.g., sink conditions. The study highlights that the selection of the in vitro release method should take into account various factors including mass transport, drug stability, data analysis and simplicity of the methodology.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: sabrine.smedegaard@sund.ku.dk.
authors.forename: Sabrine S
authors.initials: SS
authors.lastname: Jensen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: henrik.jensen@sund.ku.dk.
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark. Electronic address: ehom@novonordisk.com.
authors.forename: Eva H
authors.initials: EH
authors.lastname: Møller
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: claus.cornett@sund.ku.dk.
authors.forename: Claus
authors.initials: C
authors.lastname: Cornett
authors.affiliation: College of Pharmacy, University of Lille, 3 Rue du Professeur Laguesse, 59006 Lille, France. Electronic address: florence.siepmann@univ-lille2.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Siepmann
authors.affiliation: College of Pharmacy, University of Lille, 3 Rue du Professeur Laguesse, 59006 Lille, France. Electronic address: juergen.siepmann@univ-lille2.fr.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Siepmann
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: jesper.ostergaard@sund.ku.dk.
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry; D004343:Drug Implants; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008962:Models, Theoretical; D012996:Solutions; D040521:Subcutaneous Tissue / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D020100:Hydrogels; D007328:Insulin; D008055:Lipids; D012996:Solutions
keywords: Controlled release; Hydrogel; In vitro release methodology; Insulin; Lipid implant; UV imaging