title: Investigation of process temperature and screw speed on properties of a pharmaceutical solid dispersion using corotating and counter-rotating twin-screw extruders.
abstract: OBJECTIVE
  The use of corotating twin screw hot-melt extruders to prepare amorphous drug/polymer systems has become commonplace. As small molecule drug candidates exiting discovery pipelines trend towards higher MW and become more structurally complicated, the acceptable operating space shifts below the drug melting point. The objective of this research is to investigate the extrusion process space, which should be selected to ensure that the drug is solubilized in the polymer with minimal thermal exposure, is critical in ensuring the performance, stability and purity of the solid dispersion.
  
  
  METHODS
  The properties of a model solid dispersion were investigated using both corotating and counter-rotating hot-melt twin-screw extruders operated at various temperatures and screw speeds. The solid state and dissolution performance of the resulting solid dispersions was investigated and evaluated in context of thermodynamic predictions from Flory-Huggins Theory. In addition, the residence time distributions were measured using a tracer, modelled and characterized.
  
  
  RESULTS
  The amorphous content in the resulting solid dispersions was dependent on the combination of screw speed, temperature and operating mode.
  
  
  CONCLUSIONS
  The counter-rotating extruder was observed to form amorphous solid dispersions at a slightly lower temperature and with a narrower residence time distribution, which also exhibited a more desirable shape.
authors.affiliation: College of Pharmacy, The University of Texas at Austin, Austin, TX, USA; DisperSol Technologies, Georgetown, TX, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Keen
authors.forename: Charlie
authors.initials: C
authors.lastname: Martin
authors.forename: Augie
authors.initials: A
authors.lastname: Machado
authors.forename: Harpreet
authors.initials: H
authors.lastname: Sandhu
authors.forename: James W
authors.initials: JW
authors.lastname: McGinity
authors.forename: James C
authors.initials: JC
authors.lastname: DiNunzio
mesh_terms: D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry* / Q000592:standards; D004339:Drug Compounding / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D015736:Felodipine / Q000008:administration & dosage / Q000737:chemistry*; D005615:Freezing; D006358:Hot Temperature; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D013696:Temperature; D013816:Thermodynamics
chemical_list: D004337:Drug Carriers; D011108:Polymers; D012996:Solutions; D015736:Felodipine
keywords: amorphous; dissolution; solid dispersion; thermal processing; twin-screw melt extrusion