title: Melt granulation in fluidized bed: a comparative study of spray-on versus in situ procedure.
abstract: OBJECTIVE
  The aim of this study was to investigate the influence of process parameters, binder content and binder addition method on characteristics of the granules obtained by melt granulation (MG) in fluidized bed.
  
  
  METHODS
  Spray-on experiments were performed according to 2(3) full factorial design. The effect of binder content, molten binder feed rate, and spray air pressure on granule size and size distribution, granule shape, ﬂowability and drug release rate was investigated. In the in situ experiments, the influence of binder particle size and binder content was evaluated. Solid-state characterization was performed by means of differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy.
  
  
  RESULTS
  Size of the granules obtained by spray-on procedure was significantly influenced by binder content and spray air pressure, while the width of particle size distribution was mainly affected by binder feed rate. Spray air pressure showed the most significant influence on granule shape. It was shown that smooth and spherical particles with good flow properties may be obtained by both procedures, spray-on and in situ MG. The results obtained indicated the influence of agglomeration mechanism on granule sphericity, with higher degree of granule sphericity observed when immersion and layering was the dominant mechanism. Paracetamol release from granulates was very rapid, but after compression of the granules into tablets, drug release was considerably slower. Solid-state analysis confirmed that the physical form of the granulate components remained unaffected after the MG process.
  
  
  CONCLUSIONS
  The results presented indicate that MG in fluidized bed could be a good alternative to conventional granulation techniques.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade , Belgrade , Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mašić
authors.forename: Ilija
authors.initials: I
authors.lastname: Ilić
authors.forename: Rok
authors.initials: R
authors.lastname: Dreu
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ibrić
authors.forename: Jelena
authors.initials: J
authors.lastname: Parojčić
authors.forename: Stanko
authors.initials: S
authors.lastname: Srčič
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D013607:Tablets; D000082:Acetaminophen