title: Intra-articular injection of morphine to the horse: establishment of an in vitro-in vivo relationship.
abstract: BACKGROUND
  In the area of parenteral depots, a strong need exists for the development of suitable in vitro drug release models that might enable establishment of in vitro-in vivo relations (IVIVRs).
  
  
  OBJECTIVE
  The objective of this study was to investigate the possibility of establishing an IVIVR between morphine disappearance from the joint cavity and in vitro release data obtained employing the rotating dialysis cell model.
  
  
  METHODS
  In vitro release experiments were conducted using the rotating dialysis cell model. For establishment of an IVIVR, data from a previous study on pharmacokinetics of intra-articular (IA) morphine in horses with lipopolysaccharide-induced synovitis were used (Lindegaard et al., (2009). Vet Anaesth Analg, 37, 186-195).
  
  
  RESULTS
  A rate constant of morphine disappearance from the donor phase of the in vitro model of 1.8 × 10(-2) min(-1) was calculated, independently of the different release media used. The in vivo synovial fluid disappearance rate constants were in the range of 1.0 × 10(-2)-1.7 × 10(-2) min(-1). An IVIVR (R(2) = 0.89) was established between the calculated disappearance data and the joint disappearance data.
  
  
  CONCLUSIONS
  The results indicate that the IA fate of morphine administered in the form of a solution can be predicted from the in vitro release data obtained in the rotating dialysis cell model. Thus, this model might be a valuable tool in the establishment of IVIVRs after IA administration of drugs with similar properties.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen Ø, Denmark.
authors.forename: Anna Buus
authors.initials: AB
authors.lastname: Frost
authors.forename: Casper
authors.initials: C
authors.lastname: Lindegaard
authors.forename: Frank
authors.initials: F
authors.lastname: Larsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Susan Weng
authors.initials: SW
authors.lastname: Larsen
authors.forename: Claus
authors.initials: C
authors.lastname: Larsen
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D006736:Horses; D007270:Injections, Intra-Articular; D023421:Models, Animal; D008962:Models, Theoretical; D009020:Morphine / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine