title: Detecting Blending End-Point Using Mean Squares Successive Difference Test and Near-Infrared Spectroscopy.
abstract: An algorithm based on mean squares successive difference test applied to near-infrared and principal component analysis scores was developed to monitor and determine the blending profile and to assess the end-point in the statistical stabile phase. Model formulations consisting of an active compound (acetylsalicylic acid), together with microcrystalline cellulose and two grades of calcium carbonate with dramatically different particle shapes, were prepared. The formulation comprising angular-shaped calcium carbonate reached blending end-point slower when compared with the formulation comprising equant-shaped calcium carbonate. Utilizing the ring shear test, this distinction in end-point could be related to the difference in flowability of the formulations. On the basis of the two model formulations, a design of experiments was conducted to characterize the blending process by studying the effect of CaCO3 grades and fill level of the bin on blending end-point. Calcium carbonate grades, fill level, and their interaction were shown to have a significant impact on the blending process.
authors.affiliation: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Milad
authors.initials: M
authors.lastname: Khorasani
authors.affiliation: Faculty of Science, Department of Food Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: José M
authors.initials: JM
authors.lastname: Amigo
authors.affiliation: Takeda Pharma A/S, Roskilde, Denmark.
authors.forename: Poul
authors.initials: P
authors.lastname: Bertelsen
authors.affiliation: Faculty of Science, Department of Food Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Frans
authors.initials: F
authors.lastname: Van Den Berg
authors.affiliation: Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001241:Aspirin / Q000737:chemistry*; D002119:Calcium Carbonate / Q000737:chemistry*; D002138:Calibration; D002482:Cellulose / Q000737:chemistry*; D003658:Decision Making, Computer-Assisted; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D011208:Powders; D025341:Principal Component Analysis; D011786:Quality Control; D015203:Reproducibility of Results; D012212:Rheology; D033081:Shear Strength; D019265:Spectroscopy, Near-Infrared; D013223:Statistics as Topic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011208:Powders; D002482:Cellulose; D002119:Calcium Carbonate; C109691:microcrystalline cellulose; D001241:Aspirin
keywords: UV-Vis spectroscopy; blend uniformity analysis; blending; design of experiments; mean squares successive difference test; mixing; multivariate analysis; near-infrared spectroscopy; principal component analysis; process analytical technology (PAT); ring shear testing