title: Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.
abstract: OBJECTIVE
  This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus.
  
  
  METHODS
  Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug.
  
  
  RESULTS
  It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed.
  
  
  CONCLUSIONS
  Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: An-Katrien
authors.initials: AK
authors.lastname: Vynckier
authors.affiliation: CONEXUS Pharma, Ghent, Belgium.
authors.forename: Jody
authors.initials: J
authors.lastname: Voorspoels
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004339:Drug Compounding; D005907:Gliclazide / Q000737:chemistry*; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000737:chemistry*; D007700:Kinetics; D008687:Metformin / Q000737:chemistry*; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D011091:Polyesters; C016240:polycaprolactone; D008687:Metformin; D011205:Povidone; D005907:Gliclazide
keywords: continuous production; fixed-dose combination product; hot-melt co-extrusion; sustained release