title: Effect of plasticiser type on the hot melt extrusion of venlafaxine hydrochloride.
abstract: OBJECTIVE
  During hot melt extrusion (HME), phase changes and interactions due to thermo-mechanical stresses affect the drug incorporation into polymeric matrices. Two HME compositions of venlafaxine HCl with Eudragit RSPO (Evonic, Darmstadt, Germany) as the matrix polymer and either citric acid monohydrate (CAMH) or Lutrol F127 (BASF, Ludwigshafen, Germany) as plasticisers were compared.
  
  
  METHODS
  Miscibility and extrusion temperatures were elucidated based on solubility parameters and differential scanning calorimetry. Thermal changes in the extruded melts and their respective physical mixtures were compared. Powder X-ray diffraction was applied to detect changes in crystallinity and fourier transform infrared (FT-IR) spectroscopy for chemical interactions.
  
  
  RESULTS
  Both plasticisers (15%) enabled extrusion easily. With Lutrol, the drug remained crystalline, whereas with CAMH a single-phase amorphous transparent extrudate was obtained. Differences between the thermographs of extruded and physical mixtures indicated the importance of mechanical stresses in the single-screw extruder. In the FT-IR spectrum of Eudragit/CAMH/drug extrudate, the abscence of the peak due to venlafaxine OH and the merging of the two peaks due to CAMH carbonyl, into one, indicated esterification.
  
  
  CONCLUSIONS
  CAMH and Lutrol have different reactivities towards venlafaxine HCl and also different plasticising mechanisms for Eudragit RSPO because of hydrogen bonding and because of similar overall molecular attractive forces, respectively.
authors.affiliation: Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Melina
authors.initials: M
authors.lastname: Bounartzi
authors.forename: Athanasia
authors.initials: A
authors.lastname: Panagopoulou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kantiranis
authors.forename: Stavros
authors.initials: S
authors.lastname: Malamataris
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nikolakakis
mesh_terms: D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry*; D003460:Crystallization; D003511:Cyclohexanols / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004951:Esterification; D005615:Freezing; D006358:Hot Temperature; D006801:Humans; D010968:Plasticizers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D013314:Stress, Mechanical; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D004337:Drug Carriers; C496966:Eudragit RSPO; C506200:Lutrol; D010968:Plasticizers; D011109:Polymethacrylic Acids; D019343:Citric Acid; D011092:Polyethylene Glycols; D000069470:Venlafaxine Hydrochloride
keywords: DSC; FT-IR; PXRD; hot melt extrusion; venlafaxine hydrochloride