title: Continuous low-dose feeding of highly active pharmaceutical ingredients in hot-melt extrusion.
abstract: BACKGROUND
  Manufacturing solid low-dose pharmaceutical products has always the homogeneity challenge. In continuous manufacturing, there is the additional challenge of feeding active pharmaceutical ingredient (API) dry powder at low rates. This paper presents a method for feeding API particles into a continuous extrusion process using a suspension. The challenges for feeding and the product homogeneity are both addressed.
  
  
  OBJECTIVE
  The objective of this study is to demonstrate the feasibility of manufacturing low-dose extrudates by feeding the API particles in a diluted anti-solvent suspension.
  
  
  METHODS
  Extrudates with an Ibuprofen content of 0.021% and 0.043% (w/w) were prepared by feeding a 0.9% w/w suspension of Ibuprofen particles into a Coperion extruder.
  
  
  CONCLUSIONS
  The homogeneity (RSD) of extrudates was tested during a time span of 30 min and had values between 2% and 7%.
  
  
  CONCLUSIONS
  Feeding particles in an anti-solvent suspension offers a simple feeding option for API and minor components which yield products of desired homogeneity. The liquid feeding approach offers a simplified process with enhanced process control possibilities.
authors.affiliation: a Research Center Pharmaceutical Engineering GmbH , Graz , Austria ;
authors.forename: Marcos
authors.initials: M
authors.lastname: Llusa
authors.affiliation: a Research Center Pharmaceutical Engineering GmbH , Graz , Austria ;
authors.forename: Stefan
authors.initials: S
authors.lastname: Mohr
authors.affiliation: a Research Center Pharmaceutical Engineering GmbH , Graz , Austria ;
authors.forename: Ramona
authors.initials: R
authors.lastname: Baumgartner
authors.affiliation: a Research Center Pharmaceutical Engineering GmbH , Graz , Austria ;
authors.forename: Amrit
authors.initials: A
authors.lastname: Paudel
authors.affiliation: a Research Center Pharmaceutical Engineering GmbH , Graz , Austria ;
authors.forename: Gerold
authors.initials: G
authors.lastname: Koscher
authors.affiliation: a Research Center Pharmaceutical Engineering GmbH , Graz , Austria ;|b Institute for Particle and Process Engineering , Graz University of Technology , Graz , Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Khinast
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D006358:Hot Temperature; D007052:Ibuprofen / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013535:Suspensions / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders; D012997:Solvents; D013535:Suspensions; D007052:Ibuprofen
keywords: API homogeneity; continuous manufacturing; hot-melt extrusion; liquid feeding; low-dose solid products