title: Commercial scale validation of a process scale-up model for lubricant blending of pharmaceutical powders.
abstract: An experimental study was conducted to verify that lubrication mixing in commercial-scale bin blenders can be described by a previously-reported lubrication blending process scale-up model. Specifically, the mixing of two placebo formulations (2:1 MCC:lactose, and 2:1 MCC:DCP) with 1% magnesium stearate in 100, 400, and 2000 L bin blenders at 30% and 70% blend fill levels for several extents of lubricant mixing was examined. The lubricated powder blends were assessed for bulk/tapped density and powder flow, as measured by Hausner's ratio. The blends were then compressed into tablets and evaluated for tensile strength, friability, and disintegration. It was observed that the lubrication rate constant, γ, for tablet tensile strength and for bulk specific volume were similar. Furthermore, powder flow, as measured by Hausner's ratio, improved with increased extent of lubrication. Tablet disintegration and tablet friability were both minimally affected as a result of extended lubrication for the placebos blends evaluated in this study. The results of this study confirm that the lubrication mixing model can be applied to scale-up the lubrication blending process from batches made in 30 mL bottle blenders to batches made in 2000 L bin blenders, which is a range of nearly five orders of magnitude.
authors.affiliation: Drug Product Design, Pfizer Worldwide Research and Development, Eastern Point Road, MS 8156-033, Groton, CT 06340, USA. Electronic address: joseph.kushner@pfizer.com.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kushner
authors.affiliation: Pfizer Global Supply, Freiburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schlack
mesh_terms: D000465:Algorithms; D002130:Calcium Phosphates / Q000737:chemistry*; D002482:Cellulose / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D019245:Compressive Strength; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry*; D054327:Lubricants / Q000737:chemistry*; D008153:Lubrication; D055595:Mechanical Phenomena; D008956:Models, Chemical; D010592:Pharmaceutic Aids / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011786:Quality Control; D015203:Reproducibility of Results; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D013718:Tensile Strength
chemical_list: D002130:Calcium Phosphates; D005079:Excipients; D054327:Lubricants; D010592:Pharmaceutic Aids; D004364:Pharmaceutical Preparations; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; D002482:Cellulose; D007785:Lactose; C485829:calcium phosphate, dibasic, anhydrous; C109691:microcrystalline cellulose
keywords: Bulk specific volume; Lubrication; Magnesium stearate; Scale-up; Tablet; Tensile strength