title: Impact of microcrystalline cellulose material attributes: a case study on continuous twin screw granulation.
abstract: The International Conference on Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of material attributes, manufacturing process options and process parameters. The present case study evaluates the effect of unspecified variability of raw material properties upon the quality attributes of granules; produced using a continuous from-powder-to-tablet wet granulation line (ConsiGma™ 25). The impact of different material attributes of six samples of microcrystalline cellulose (MCC) was investigated. During a blind study the different samples of MCC were used separately and the resulting granules were evaluated in order to identify the differences between the six samples. Variation in size distribution due to varying water binding capacity of the MCC samples was observed. The cause of this different water binding capacity was investigated and was caused by a different degree of crystallinity. Afterwards, an experimental design was conducted in order to evaluate the effect of both product and process variability upon the granule size distribution. This model was used in order to calculate the required process parameters to obtain a preset granule size distribution regardless of the type of MCC used. The difference in water binding capacity and its effect on granular properties was still present when combining the MCC grades with different binders.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.
authors.forename: Margot
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Ana
authors.initials: A
authors.lastname: Correia
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Plecker
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Department of Pharmaceutical Technology, University of Ljubljana, Aškerčeva 7, Ljubljana, Slovenia.
authors.forename: Ilija
authors.initials: I
authors.lastname: Ilić
authors.affiliation: Division of Glycoscience, School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Centre, Stockholm, Sweden.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: FMC R&D and Application Center, Avenue Mounier 83, Brussels, Belgium.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Onofre
authors.affiliation: Division of Glycoscience, School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Centre, Stockholm, Sweden.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bulone
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium. Electronic address: Thomas.DeBeer@Ugent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002482:Cellulose / Q000032:analysis / Q000737:chemistry*; D008962:Models, Theoretical; D010316:Particle Size; D011208:Powders; D012212:Rheology; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000032:analysis / Q000737:chemistry
chemical_list: D011208:Powders; D014867:Water; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: MCC; Quality by design; Raw material variability; Twin screw granulation; Water binding capacity