title: Effect of ultra-high pressure homogenization on the interaction between bovine casein micelles and ritonavir.
abstract: OBJECTIVE
  The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT).
  
  
  METHODS
  Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release.
  
  
  RESULTS
  Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment.
  
  
  CONCLUSIONS
  Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications.
authors.affiliation: Department of Food Science and Technology, The University of Tennessee, 2605 River Dr., Knoxville, Tennessee, 37996-4539, USA.
authors.forename: M
authors.initials: M
authors.lastname: Corzo-Martínez
authors.forename: M
authors.initials: M
authors.lastname: Mohan
authors.forename: J
authors.initials: J
authors.lastname: Dunlap
authors.forename: F
authors.initials: F
authors.lastname: Harte
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002364:Caseins / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D011312:Pressure; D011485:Protein Binding; D012212:Rheology; D019438:Ritonavir / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D002364:Caseins; D004337:Drug Carriers; D017320:HIV Protease Inhibitors; D008823:Micelles; D011208:Powders; D019438:Ritonavir