title: "Micro to macro (M2M)"--A novel approach for intravenous delivery of propofol.
abstract: OBJECTIVE
  Propofol emulsions have limited shelf life and safety concerns for injection. Microemulsions of propofol are thermodynamically stable and simpler to manufacture, but cause additional pain on injection. We propose a novel micro to macro (M2M) approach of destabilizing a microemulsion immediately prior to injection.
  
  
  METHODS
  Microemulsions of propofol were prepared at two to three times the drug loadings of commercial formulations. We determined suitable microemulsion compositions which destabilize into macroemulsions after two or three fold dilutions with water. Droplet growth after dilution was measured with dynamic light scattering. Increasing solution turbidity after dilution was also measured optically with millisecond resolution. Experimental data was analyzed in the context of a coalescence model.
  
  
  RESULTS
  Microemulsions rapidly coalesce into larger droplet size macroemulsions after dilution according to the phase diagram shift. The resulting macroemulsions are metastable retaining their droplet size for several hours. Droplet growth occurs on the order of seconds and a metastable size of about 1 micron is reached in minutes. Rates of droplet growth and metastable droplet sizes depend on the surfactant composition. The coalescence model predicts droplet growth with good agreement but only after accounting for the finite probability of coalescence from each collision.
  
  
  CONCLUSIONS
  The M2M concept has been demonstrated for the anesthetic drug propofol which may improve stability and manufacturability in addition to reducing pain on injection. This approach could be adapted to other hydrophobic vesicant drugs as well.
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Damitz
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA. Electronic address: Chauhan@che.ufl.edu.
authors.forename: Anuj
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry*; D015742:Propofol / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D018686:Anesthetics, Intravenous; D004655:Emulsions; D015742:Propofol
keywords: Coalescence; Formulation; Interfacial phenomena; Microemulsion; Propofol; Surfactant