title: Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems.
abstract: OBJECTIVE
  To develop a high-throughput in vitro intestinal lipolysis (HTP) model, without any means of pH-stat-titration, to enable a fast evaluation of lipid-based drug delivery systems (LbDDS).
  
  
  METHODS
  The HTP model was compared to the traditionally used dynamic in vitro lipolysis (DIVL) model with regard to the extent of lipid digestion and drug distribution of two poorly soluble model drugs (cinnarizine and danazol), during digestion of three LbDDS (LbDDS I-III).
  
  
  RESULTS
  The HTP model was able to maintain pH around 6.5 during digestion, without the addition of NaOH to neutralize the free fatty acids (FFAs), due to an increased buffer capacity. Cinnarizine was primarily located in the aqueous phase during digestion of all three LbDDS and did not differ significantly between the two models. The distribution of danazol varied from formulation to formulation, but no significant difference between the models was observed. The triacylglycerides (TAG) in LbDDS III were digested to the same extent in both models, whereas the TAG present in LbDDS II was digested slightly less in the HTP model. No TAG was present in LbDDS I and digestion was therefore not analyzed.
  
  
  CONCLUSIONS
  The HTP model is able to predict drug distribution during digestion of LbDDS containing poorly water soluble drugs in the same manner as the DIVL model. Thus the HTP model might prove applicable for high-throughput evaluation of LbDDS in e.g. 96 well plates or small scale dissolution equipment.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Denmark.
authors.forename: Mette D
authors.initials: MD
authors.lastname: Mosgaard
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Denmark.
authors.forename: Philip
authors.initials: P
authors.lastname: Sassene
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Denmark.
authors.forename: Huiling
authors.initials: H
authors.lastname: Mu
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Denmark; Bioneer: FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: anette.mullertz@sund.ku.dk.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002936:Cinnarizine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D003613:Danazol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D057166:High-Throughput Screening Assays / Q000379:methods*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008066:Lipolysis; D008954:Models, Biological; D010316:Particle Size
chemical_list: D004337:Drug Carriers; D008055:Lipids; D002936:Cinnarizine; D003613:Danazol
keywords: In vitro lipolysis; Lipid based drug delivery systems; Poorly soluble drugs