title: Study of granule growth kinetics during in situ fluid bed melt granulation using in-line FBRM and SFT probes.
abstract: OBJECTIVE
  The aim of this work was to study the granule growth kinetics during in situ fluid bed melt granulation process using real-time particle size measurement techniques. In addition, the usefulness of these techniques during scale-up of melt granulation was evaluated.
  
  
  METHODS
  Focused beam reflectance measurement (FBRM) and spatial filtering technique (SFT) probes were used within the process chamber of fluid bed granulator for real-time in-line granule size analysis.
  
  
  RESULTS
  The results demonstrated that the use of in-line particle size probes in fluid bed granulator during the process offers an insightful view of granule growth and allows in-process monitoring of granule chord length changes. The effect of selected critical parameters (binder content, inlet air temperature and product endpoint temperature) on the granule growth was clearly presented by in-line measurements in a laboratory scale. A comparison of granule size measurements from both FBRM and SFT probes showed similar particle growth trends, which were in close correlation to the product temperature. Comparable trends in end granule particle size were observed when comparing different in-line, at-line and off-line particle size measurements.
  
  
  CONCLUSIONS
  The in-line FBRM and SFT probes were successfully employed in in situ fluid bed melt granulation process to study the influence of critical formulation/process parameters on the granule growth kinetics. The scale-up experiment confirmed the potential of these in-line granule size measurement techniques as a viable tool for process monitoring during the transfer of granulation to the larger scale or another manufacturing site/equipment.
authors.affiliation: Krka, d.d., Novo mesto , Research and Development , Slovenia and.
authors.forename: Simon
authors.initials: S
authors.lastname: Kukec
authors.forename: Grega
authors.initials: G
authors.lastname: Hudovornik
authors.forename: Rok
authors.initials: R
authors.lastname: Dreu
authors.forename: Franc
authors.initials: F
authors.lastname: Vrečer
mesh_terms: D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000737:chemistry*; D000077261:Carvedilol; D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D011412:Propanolamines / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D002227:Carbazoles; D005079:Excipients; D011208:Powders; D011412:Propanolamines; D000077261:Carvedilol; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: Carvedilol; chord length; critical formulation/process parameters; in-line granule size measurements; process understanding and monitoring; scale-up