title: In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions.
abstract: As the number of applications for polymers in pharmaceutical development is increasing, there is need for fundamental understanding on how such compounds behave during tableting. This research is focussed on the tableting behaviour of amorphous polymers, their solid dispersions and the impact of hot-melt extrusion on the compaction properties of these materials. Soluplus, Kollidon VA 64 and Eudragit EPO were selected as amorphous polymers since these are widely studied carriers for solid dispersions, while Celecoxib was chosen as BCS class II model drug. Neat polymers and physical mixtures (up to 35% drug load) were processed by hot-melt extrusion (HME), milled and sieved to obtain powders with comparable particle sizes as the neat polymer. A novel approach was used for in-line analysis of the compaction properties on a rotary tablet press (Modul P, GEA) using complementary sensors and software (CDAAS, GEA). By combining 'in-die' and 'out-of-die' techniques, it was possible to investigate in a comprehensive way the impact of HME on the tableting behaviour of amorphous polymers and their formulations. The formation of stable glassy solutions altered the formulations towards more fragmentary behaviour under compression which was beneficial for the tabletability. Principal component analysis (PCA) was applied to summarize the behaviour during compaction of the formulations, enabling the selection of Soluplus and Kollidon VA 64 as the most favourable polymers for compaction of glassy solutions.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Grymonpré
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Verstraete
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Bockstal
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van Renterghem
authors.affiliation: Department of Electronics and Information Systems (ELIS), Ghent University, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Rombouts
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000068579:Celecoxib / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D006358:Hot Temperature; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D011312:Pressure; D011759:Pyrrolidines / Q000737:chemistry*; D012212:Rheology; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000706:statistics & numerical data; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D011108:Polymers; D011109:Polymethacrylic Acids; D011145:Polyvinyls; D011208:Powders; D011759:Pyrrolidines; D013607:Tablets; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; C518398:Eudragit E PO; D000068579:Celecoxib
keywords: Amorphous polymers; Hot-melt extrusion; In-line monitoring; Multivariate data analysis; Powder compaction; Rotary tablet press