title: Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.
abstract: OBJECTIVE
  This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated.
  
  
  METHODS
  Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates.
  
  
  RESULTS
  Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate.
  
  
  CONCLUSIONS
  Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Djuris
authors.forename: Nikolakakis
authors.initials: N
authors.lastname: Ioannis
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ibric
authors.forename: Zorica
authors.initials: Z
authors.lastname: Djuric
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Kachrimanis
mesh_terms: D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry* / Q000592:standards; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005615:Freezing; D006244:Hardness; D006358:Hot Temperature; D006801:Humans; D010968:Plasticizers / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D012996:Solutions
chemical_list: D004337:Drug Carriers; D010968:Plasticizers; D011145:Polyvinyls; D012996:Solutions; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D020442:Poloxamer; D002220:Carbamazepine; D011092:Polyethylene Glycols
keywords: Poloxamer 407; Soluplus; carbamazepine; mixture design; solid dispersion