Using Compartment Modeling to Investigate Mixing Behavior of a Continuous Mixer
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In this paper, the development of a compartment model to simulate mixing within a continuous blender is reported. The main benefit of the method is that it can generate extensive modeling predictions in very short computational time. The model can also be used to explore the effect of sampling parameters on estimated mixing performance, a topic that has been central to pharmaceutical manufacturing for the past 15 years and that remains a central issue in the PAT initiative. However, this method requires more input than conventional particle dynamics methods. Thus, we investigate the effects of modeling parameters on mixing performance to develop general guidance needed to adapt this modeling framework to any continuous process. An experimental technique based on longitudinal sampling is used to examine the content uniformity of the blend along the continuous mixer. The model compares favorably with continuous mixing experiments, capture the effects of feeding rate variability, active product ingredient concentration, and blender processing angle, while effectively capturing and making explicit the effect of sampling parameters such as number of samples and sample size. The modeling approach provides a convenient tool for process design.
KeywordsCompartment modeling Continuous powder mixing
The authors would like to thank the National Science Foundation for their financial support through grants NSF-0504497 and NSF-ECC 0540855 both to Fernando J. Muzzio as well as the Nanopharmaceutical IGERT Fellowship to Patricia M. Portillo.
- 3.Beaudry JP. Blender efficiency. Chem Eng. 1948;55:112–3.Google Scholar
- 4.Beddow JK, Meloy T. Testing and characterization of powders and fine particles. London: Heyden and Son; 1980.Google Scholar
- 17.FDA. Powder blends and finished dosage units—stratified in-process dosage unit sampling and assessment, Pharmaceutical CGMP’s, Guidance for Industry; 2003.Google Scholar
- 27.Massol-Chaudeur S, Berthiaux H, Dodds JA. Experimental study of the mixing kinetics of binary pharmaceutical powder mixtures in a laboratory hoop mixer. Chem Eng Sci. 2002;57(19, 13):4053–65.Google Scholar
- 34.Ristow GH. Flow properties of granular materials in 3D Geometries, Ph.D. Thesis, Philipps-Universitat Marburg; 1998.Google Scholar
- 35.Ross S. A first course in probability, 6th edn. Upper Saddle River, NJ: Prentice Hall; 2002.Google Scholar
- 36.Szépvölgyi J. Handbook of conveying and handling of particulate solids. Amsterdam: Elsevier Science B.V.; 2001. pp. 665–671.Google Scholar