title: Development of carvedilol-cyclodextrin inclusion complexes using fluid-bed granulation: a novel solid-state complexation alternative with technological advantages.
abstract: OBJECTIVE
  This study sought to evaluate the achievement of carvedilol (CARV) inclusion complexes with modified cyclodextrins (HPβCD and HPγCD) using fluid-bed granulation (FB).
  
  
  METHODS
  The solid complexes were produced using FB and spray drying (SD) and were characterised by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction, SEM, flowability and particle size analyses and in vitro dissolution.
  
  
  RESULTS
  The DSC, FTIR and powder X-ray diffraction findings suggested successful CARV inclusion in the modified β- and γ-cyclodextrins, which was more evident in acidic media. The CARV dissolution rate was ~7-fold higher for complexes with both cyclodextrins prepared using SD than for raw CARV. Complexes prepared with HPβCD using FB also resulted in a significant improvement in dissolution rate (~5-fold) and presented superior flowability and larger particle size.
  
  
  CONCLUSIONS
  The findings suggested that FB is the best alternative for large-scale production of solid dosage forms containing CARV. Additionally, the results suggest that HPγCD could be considered as another option for CARV complexation because of its excellent performance in inclusion complex formation in the solid state.
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Ellen C P
authors.initials: EC
authors.lastname: Alonso
authors.affiliation: Pharmaceutical Application Laboratory, Ashland Specialty Ingredients, São Paulo, SP, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Riccomini
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Luis Antônio D
authors.initials: LA
authors.lastname: Silva
authors.affiliation: Pharmaceutical Application Laboratory, Ashland Specialty Ingredients, São Paulo, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galter
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Eliana M
authors.initials: EM
authors.lastname: Lima
authors.affiliation: Pharmaceutical and Nutrition Specialties R&D, Ashland Specialty Ingredients, Wilmington, DE, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Durig
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Stephania F
authors.initials: SF
authors.lastname: Taveira
authors.affiliation: Chemical Institute, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Felipe Terra
authors.initials: FT
authors.lastname: Martins
authors.affiliation: Laboratory of Food, Drug and Cosmetics (LTMAC), School of Health Sciences, University of Brasília, Brasília, DF, Brazil.
authors.forename: Marcílio S S
authors.initials: MS
authors.lastname: Cunha-Filho
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil. ricardomarreto@ufg.br.
authors.forename: Ricardo N
authors.initials: RN
authors.lastname: Marreto
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002227:Carbazoles / Q000737:chemistry*; D000077261:Carvedilol; D004339:Drug Compounding / Q000379:methods; D010316:Particle Size; D011412:Propanolamines / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; D000077261:Carvedilol
keywords: carvedilol; hydroxypropyl-β-cyclodextrin; hydroxypropyl-γ-cyclodextrin; solid-state inclusion complex