title: Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug.
abstract: The article describes the application of a twin-screw granulation process to enhance the dissolution rate of the poorly water soluble drug, ibuprofen (IBU). A quality-by-design (QbD) approach was used to manufacture IBU loaded granules via hot-melt extrusion (HME) processing. For the purpose of the study, a design of experiment (DoE) was implemented to assess the effect of the formulation compositions and the processing parameters. This novel approach allowed the use of, polymer/inorganic excipients such as hydroxypropyl methylcellulose (HPMC) and magnesium aluminometasilicate (Neusilin(®)-MAS) with polyethylene glycol 2000 (PEG) as the binder without requiring a further drying step. IBU loaded batches were processed using a twin screw extruder to investigate the effect of MAS/polymer ratio, PEG amount (binder) and liquid to solid (L/S) ratios on the dissolution rates, mean particle size and the loss on drying (LoD) of the extruded granules. The DoE analysis showed that the defined independent variables of the twin screw granulation process have a complex effect on the measured outcomes. The solid state analysis showed the existence of partially amorphous IBU state which had a significant effect on the dissolution enhancement in acidic media. Furthermore, the analysis obtained from the surface mapping by Raman proved the homogenous distribution of the IBU in the extruded granulation formulations.
authors.affiliation: Faculty of Engineering and Science, School of Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK. Electronic address: M.Maniruzzaman@gre.ac.uk.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Maniruzzaman
authors.affiliation: Fuji Chemical Industry Co., Ltd., 12F The Front Tower Shiba Koen, 2-6-3 Shibakoen, Minato-Ward, Tokyo 105-0011 Japan.
authors.forename: Arun
authors.initials: A
authors.lastname: Nair
authors.affiliation: IUT De Rouen, IUT de Rouen, Bâtiment A-1er étage, rue Lavoisier, 76821 Mont-Saint-Aignan, CEDEX France.
authors.forename: Maxcene
authors.initials: M
authors.lastname: Renault
authors.affiliation: Faculty of Engineering and Science, School of Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
authors.forename: Uttom
authors.initials: U
authors.lastname: Nandi
authors.affiliation: Faculty of Engineering and Science, School of Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
authors.forename: Nicholaos
authors.initials: N
authors.lastname: Scoutaris
authors.affiliation: Wolfson Centre of Bulk Solid Handling, Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Farnish
authors.affiliation: Wolfson Centre of Bulk Solid Handling, Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
authors.forename: Michael S A
authors.initials: MS
authors.lastname: Bradley
authors.affiliation: Faculty of Engineering and Science, School of Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Snowden
authors.affiliation: Faculty of Engineering and Science, School of Science, University of Greenwich, Chatham Maritime, Chatham, Kent ME4 4TB, UK. Electronic address: D.Douroumis@gre.ac.uk.
authors.forename: Dennis
authors.initials: D
authors.lastname: Douroumis
mesh_terms: D017607:Aluminum Compounds / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives / Q000737:chemistry; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry; D017616:Magnesium Compounds / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D017640:Silicates / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D017607:Aluminum Compounds; D005079:Excipients; D017616:Magnesium Compounds; D017640:Silicates; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; C033065:aluminum magnesium silicate; C000595210:polyethylene glycol 2000; D007052:Ibuprofen
keywords: DVS; Dissolutions; DoE; Granulations; QbD; Raman; Twin screw