title: In vitro release from oil injectables for intra-articular administration: Importance of interfacial area, diffusivity and partitioning.
abstract: Most in vitro methods for evaluating parenteral oil based depots are focusing on intramuscular or subcutaneous injection. For intra-articular injection other mechanisms may control the overall drug release rate due to a relatively smaller interfacial area and longer transport distance of the drug substance in the oil to the oil-synovial fluid interface. In the current work, an in vitro model for testing drug release from oil solutions intended for intra-articular injection was evaluated. The release of the model drugs naproxen, piroxicam and ropivaciane from a well-defined surface area of the lipophilic solutions were followed using an in vitro model based on a modified USP II paddle apparatus with modest agitation (50rpm) of the oil formulation. By alteration of the viscosity of the oil, the oil-water interfacial area, the oil volume and the stirring efficiency of the release medium, it was shown that the drug release rate was dependent on the drug diffusivity in the oil and the degree of agitation generated in the oil vehicle. In addition, the partitioning of the drug between the oil vehicle and the release media was found to influence the release rate. In combination with an improved understanding of in vivo drug release and distribution, the present work may form a promising foundation for future in vivoin vitro correlations.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. mat@farma.ku.dk
authors.forename: Mette
authors.initials: M
authors.lastname: Thing
authors.forename: Claus
authors.initials: C
authors.lastname: Larsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.forename: Susan Weng
authors.initials: SW
authors.lastname: Larsen
mesh_terms: D000577:Amides / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007270:Injections, Intra-Articular; D008956:Models, Chemical; D009288:Naproxen / Q000737:chemistry; D009821:Oils / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D010894:Piroxicam / Q000737:chemistry; D000077212:Ropivacaine; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: D000577:Amides; D003692:Delayed-Action Preparations; D009821:Oils; D004364:Pharmaceutical Preparations; D014677:Pharmaceutical Vehicles; D014867:Water; D010894:Piroxicam; D009288:Naproxen; D000077212:Ropivacaine