title: Roller compaction scale-up using roll width as scale factor and laser-based determined ribbon porosity as critical material attribute.
abstract: Due to the complexity and difficulties associated with the mechanistic modeling of roller compaction process for scale-up, an innovative equipment approach is to keep roll diameter fixed between scales and instead vary the roll width. Assuming a fixed gap and roll force, this approach should create similar conditions for the nip regions of the two compactor scales, and thus result in a scale-reproducible ribbon porosity. In the present work a non-destructive laser-based technique was used to measure the ribbon porosity at-line with high precision and high accuracy as confirmed by an initial comparison to a well-established volume displacement oil intrusion method. The ribbon porosity was found to be scale-independent when comparing the average porosity of a group of ribbon samples (n=12) from small-scale (Mini-Pactor®) to large-scale (Macro-Pactor®). A higher standard deviation of ribbons fragment porosities from the large-scale roller compactor was attributed to minor variations in powder densification across the roll width. With the intention to reproduce ribbon porosity from one scale to the other, process settings of roll force and gap size applied to the Mini-Pactor® (and identified during formulation development) were therefore directly transferrable to subsequent commercial scale production on the Macro-Pactor®. This creates a better link between formulation development and tech transfer and decreases the number of batches needed to establish the parameter settings of the commercial process.
authors.affiliation: H. Lundbeck A/S, Biologics and Pharmaceutical Science, Ottiliavej 9, DK-2500, Valby, Denmark; NNE Pharmaplan A/S, Process Technology Consulting, Nybrovej 80, DK-2820 Gentofte, Denmark. Electronic address: MnAq@nnepharmaplan.com.
authors.forename: Morten
authors.initials: M
authors.lastname: Allesø
authors.affiliation: H. Lundbeck A/S, Biologics and Pharmaceutical Science, Ottiliavej 9, DK-2500, Valby, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Holm
authors.affiliation: H. Lundbeck A/S, Biologics and Pharmaceutical Science, Ottiliavej 9, DK-2500, Valby, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Holm
mesh_terms: D007834:Lasers; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D016062:Porosity; D011312:Pressure; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations
keywords: Direct laser measurement; Microcrystalline cellulose; Ribbon porosity; Roller compaction; Solid fraction; Volume displacement