Tags

Type your tag names separated by a space and hit enter

Commercial scale validation of a process scale-up model for lubricant blending of pharmaceutical powders.
Int J Pharm. 2014 Nov 20; 475(1-2):147-55.IJ

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Kushner J
Drug Product Design, Pfizer Worldwide Research and Development, Eastern Point Road, MS 8156-033, Groton, CT 06340, USA. Electronic address: joseph.kushner@pfizer.com.
Schlack H
Pfizer Global Supply, Freiburg, Germany.

MeSH

AlgorithmsCalcium PhosphatesCelluloseChemical PhenomenaChemistry, PharmaceuticalCompressive StrengthDrug CompoundingExcipientsLactoseLubricantsLubricationMechanical PhenomenaModels, ChemicalPharmaceutic AidsPharmaceutical PreparationsQuality ControlReproducibility of ResultsStearic AcidsTabletsTensile Strength

Pub Type(s)

Comparative Study
Journal Article
Validation Study

Language

eng

PubMed ID

25152166

Citation

Kushner, Joseph, and Holger Schlack. "Commercial Scale Validation of a Process Scale-up Model for Lubricant Blending of Pharmaceutical Powders." International Journal of Pharmaceutics, vol. 475, no. 1-2, 2014, pp. 147-55.
Kushner J, Schlack H. Commercial scale validation of a process scale-up model for lubricant blending of pharmaceutical powders. Int J Pharm. 2014;475(1-2):147-55.
Kushner, J., & Schlack, H. (2014). Commercial scale validation of a process scale-up model for lubricant blending of pharmaceutical powders. International Journal of Pharmaceutics, 475(1-2), 147-55. https://doi.org/10.1016/j.ijpharm.2014.08.036
Kushner J, Schlack H. Commercial Scale Validation of a Process Scale-up Model for Lubricant Blending of Pharmaceutical Powders. Int J Pharm. 2014 Nov 20;475(1-2):147-55. PubMed PMID: 25152166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Commercial scale validation of a process scale-up model for lubricant blending of pharmaceutical powders. AU - Kushner,Joseph,4th AU - Schlack,Holger, Y1 - 2014/08/23/ PY - 2014/06/05/received PY - 2014/07/28/revised PY - 2014/08/19/accepted PY - 2014/8/26/entrez PY - 2014/8/26/pubmed PY - 2015/8/4/medline KW - Bulk specific volume KW - Lubrication KW - Magnesium stearate KW - Scale-up KW - Tablet KW - Tensile strength SP - 147 EP - 55 JF - International journal of pharmaceutics JO - Int J Pharm VL - 475 IS - 1-2 N2 - 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. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/25152166/Commercial_scale_validation_of_a_process_scale_up_model_for_lubricant_blending_of_pharmaceutical_powders_ DB - PRIME DP - Unbound Medicine ER -