title: Investigation into mixing capability and solid dispersion preparation using the DSM Xplore Pharma Micro Extruder.
abstract: OBJECTIVE
  The goal of this investigation was to qualify the DSM Xplore Pharma Micro Extruder as a formulation screening tool for early-stage hot-melt extrusion.
  
  
  METHODS
  Dispersive and distributive mixing was investigated using soluplus, copovidone or basic butylated methacrylate copolymer with sodium chloride (NaCl) in a batch size of 5 g. Eleven types of solid dispersions were prepared using various drugs and carriers in batches of 5 g in accordance with the literature.
  
  
  RESULTS
  The dispersive mixing was a function of screw speed and recirculation time and the particle size was remarkably reduced after 1 min of processing, regardless of the polymers. An inverse relationship between the particle size and specific mechanical energy (SME) was also found. The SME values were higher than those in large-scale extruders. After 1 min recirculation at 200 rpm, the uniformity of NaCl content met the criteria of the European Pharmacopoeia, indicating that distributive mixing was achieved in this time. For the solid dispersions preparations, the results from different scanning calorimetry, powder X-ray diffractometry and in-vitro dissolution tests confirmed that all solid-dispersion systems were successfully prepared.
  
  
  CONCLUSIONS
  These findings demonstrated that the extruder is a useful tool to screen solid-dispersion formulations and their material properties on a small scale.
authors.affiliation: Pharmaceutical Research and Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sakai
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D005615:Freezing; D006358:Hot Temperature; D006801:Humans; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D012996:Solutions / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011145:Polyvinyls; D011759:Pyrrolidines; D012996:Solutions; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D012965:Sodium Chloride
keywords: dispersive mixing; distributive mixing; formulation screening; melt extrusion; small scale extruder; solid dispersion