title: A novel methodology to study polymodal particle size distributions produced during continuous wet granulation.
abstract: It is important during powder granulation to obtain particles of a homogeneous size especially in critical situations such as pharmaceutical manufacture. To date, homogeneity of particle size distribution has been defined by the use of the d50combined with the span of the particle size distribution, which has been found ineffective for polymodal particle size distributions. This work focuses on demonstrating the limitations of the span parameter to quantify homogeneity and proposes a novel improved metric based on the transformation of a typical particle size distribution curve into a homogeneity factor which can vary from 0 to 100%. The potential of this method as a characterisation tool has been demonstrated through its application to the production of granules using two different materials. The workspace of an 11mm twin screw granulator was defined for two common excipients (α-lactose monohydrate and microcrystalline cellulose). Homogeneity of the obtained granules varied dramatically from 0 to 95% in the same workspace, allowing identification of critical process parameters (e.g. feed rate, liquid/solid ratio, torque velocities). In addition it defined the operational conditions required to produce the most homogeneous product within the range 5μm-2.2mm from both materials.
authors.affiliation: EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC), University of Strathclyde, Technology and Innovation Centre, 99 George Street, G1 1RD Glasgow, United Kingdom; Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, G4 0RE Glasgow, United Kingdom. Electronic address: carlota.mendez@strath.ac.uk.
authors.forename: Carlota
authors.initials: C
authors.lastname: Mendez Torrecillas
authors.affiliation: EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC), University of Strathclyde, Technology and Innovation Centre, 99 George Street, G1 1RD Glasgow, United Kingdom; Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, G4 0RE Glasgow, United Kingdom.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Halbert
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, G4 0RE Glasgow, United Kingdom; Medway School of Pharmacy, University of Kent, Medway Campus, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, United Kingdom. Electronic address: D.Lamprou@kent.ac.uk.
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Lamprou
mesh_terms: D002482:Cellulose; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D011208:Powders; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Granules; Homogeneity factor; Particle size distribution; Quality by design; Twin screw granulation