title: New immediate release formulation for deterring abuse of methadone.
abstract: BACKGROUND
  Drug abusers are known to take a dosage form containing an opioid analgesic and crush, shear, grind, chew, or dissolve it in water or in alcohol, in order to extract the opioid component.
  
  
  OBJECTIVE
  Develop an anti abuse immediate release formulation using methadone as model drug.
  
  
  METHODS
  Tablets combining methadone and alkalizing agents were manufactured. A methadone assay was used to determine extraction efficiency from tablets in aqueous and alcohol solvents. In vitro dissolution testing was used to determine drug release in different media.
  
  
  CONCLUSIONS
  Meglumine-based formulations prevented extraction of 70 to 100% of methadone from tablets. Addition of this alkalizing agent caused methadone to precipitate out of a solution along with other ingredients and be retained on standard filters. Meglumine-containing and control tablets showed similar dissolution profiles in acidic media, suggesting adequate solubilisation of the drug early in the gastrointestinal tract. Finally, stability upon storage of the formulations for 6 months at 25°C/60%RH and 40°C/75%RH was confirmed.
  
  
  CONCLUSIONS
  Incorporation of an alkalizing agent into methadone tablets significantly reduced the preparation of a methadone solution for intravenous administration and abuse, while allowing the formulation to release methadone in gastric media and provide desired pharmacological effect.
authors.affiliation: Pharmaceutical Research and Development, Corealis Pharma Inc., Laval, Qc, Canada.
authors.forename: A O
authors.initials: AO
authors.lastname: Betancourt
authors.forename: P M
authors.initials: PM
authors.lastname: Gosselin
authors.forename: R K
authors.initials: RK
authors.lastname: Vinson
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D008691:Methadone / Q000737:chemistry*; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013607:Tablets / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D013607:Tablets; D014867:Water; D000431:Ethanol; D008691:Methadone