title: Use of the channel fill level in defining a design space for twin screw wet granulation.
abstract: Twin screw wet granulation is a key process in the continuous manufacture of oral solid dosage forms. Previous research has qualitatively suggested that the channel fill level influences the granules produced. In this paper a quantitative measure of the total volumetric fraction of the conveying element channels of the screw filled with powder (φ) was used. Experimental results are shown which demonstrate that very similar particle size distributions can be obtained at the same φ with the same material and screw configuration but radically different solids feed rates and screw speeds. Morphology of the granules also correlates with φ. This is consistent with previous observations in the literature correlating granule attributes with powder feed rate and screw speed but also considers the two parameters in combination. A process design space approach based on φ is proposed. This can be determined empirically, and potentially has value in setting process control strategies, assuring process robustness and allowing process flexibility during the product lifecycle.
authors.affiliation: GSK, New Frontiers Science Park, Harlow, CM19 5AW, United Kingdom. Electronic address: lee.j.gorringe@gsk.com.
authors.forename: L J
authors.initials: LJ
authors.lastname: Gorringe
authors.affiliation: GSK, New Frontiers Science Park, Harlow, CM19 5AW, United Kingdom.
authors.forename: G S
authors.initials: GS
authors.lastname: Kee
authors.affiliation: GSK, New Frontiers Science Park, Harlow, CM19 5AW, United Kingdom.
authors.forename: M F
authors.initials: MF
authors.lastname: Saleh
authors.affiliation: GSK, New Frontiers Science Park, Harlow, CM19 5AW, United Kingdom.
authors.forename: N H
authors.initials: NH
authors.lastname: Fa
authors.affiliation: GSK, New Frontiers Science Park, Harlow, CM19 5AW, United Kingdom.
authors.forename: R G
authors.initials: RG
authors.lastname: Elkes
mesh_terms: D004304:Dosage Forms; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D004304:Dosage Forms; D011208:Powders
keywords: Channel fill; Continuous manufacturing; Design space; Residence time; Twin screw granulation