Moisture soft sensor for batch fluid bed dryers: A practical approach

Abstract Moisture content is a critical quality attribute in drying of pharmaceutical formulations. This paper proposes a hybrid soft sensor for online real-time estimation of the product moisture in batch fluid bed dryers. Major applications include end-point detection, feed-back control, and process optimization resulting from increased process understanding. The proposed soft sensor utilizes commonly available measurements in a hybrid first-principle/empirical mathematical framework with few parameters to calibrate. Each parameter has a physical meaning in the model, enabling quantitative comparison of the drying dynamics of different formulations, products, and equipment. The soft sensor model requires experimental data from few batches for calibration, and historical data from production batches can be used for this purpose when available. Three case studies, two in pilot plant using different formulations and one using historical data from manufacturing batches, are presented in this paper. The results support the proposed soft sensor model as a robust, practical and accurate method for online estimation of moisture in fluid bed dryers.

[1]  S. Jeong,et al.  Effects of moisture content and compression pressure of various deforming granules on the physical properties of tablets , 2017 .

[2]  Chonghun Han,et al.  Clustering-Based Hybrid Soft Sensor for an Industrial Polypropylene Process with Grade Changeover Operation , 2005 .

[3]  Lipika Chablani,et al.  Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process , 2011, AAPS PharmSciTech.

[4]  J. Rantanen,et al.  Use of the Near-Infrared Reflectance Method for Measurement of Moisture Content During Granulation , 2000, Pharmaceutical development and technology.

[5]  Adnan Midilli,et al.  Single layer drying behaviour of potato slices in a convective cyclone dryer and mathematical modeling , 2003 .

[6]  Cedric Briens,et al.  Continuous on-line measurement of solid moisture content during fluidized bed drying using triboelectric probes , 2008 .

[7]  Wuqiang Yang,et al.  Online measurement and control of solids moisture in fluidised bed dryers , 2009 .

[8]  Feridun Hamdullahpur,et al.  Thermodynamic modeling of fluidized bed drying of moist particles , 2003 .

[9]  Dale E. Seborg,et al.  Optimal selection of soft sensor inputs for batch distillation columns using principal component analysis , 2005 .

[10]  A. Mujumdar Book Review: Handbook of Industrial Drying, Third Edition , 2007 .

[11]  Heartwin A. Pushpadass,et al.  Influence of moisture content on the flow properties of basundi mix , 2017 .

[12]  T. De Beer,et al.  Analysing drying unit performance in a continuous pharmaceutical manufacturing line by means of mass--energy balances. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  Ingmar Nopens,et al.  Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[14]  P. Senior,et al.  Investigation of batch fluidized-bed drying by mathematical modeling, CFD simulation and ECT measurement , 2008 .

[15]  Felicia Nkem Ihunegbo,et al.  Acoustic chemometrics for on-line monitoring and end-point determination of fluidised bed drying , 2013 .

[16]  Bogdan Gabrys,et al.  Data-driven Soft Sensors in the process industry , 2009, Comput. Chem. Eng..

[17]  Bodhisattwa Chaudhuri,et al.  Contact drying: a review of experimental and mechanistic modeling approaches. , 2012, International journal of pharmaceutics.

[18]  Sten Bay Jørgensen,et al.  A systematic approach for soft sensor development , 2007, Comput. Chem. Eng..

[19]  T. De Beer,et al.  Mechanistic modelling of fluidized bed drying processes of wet porous granules: a review. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[20]  Claas Döscher,et al.  In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[21]  A. Marzocchella,et al.  Fluidised bed drying of powdered materials: Effects of operating conditions , 2017 .

[22]  Hamidreza Mehdizadeh,et al.  Generic Raman‐based calibration models enabling real‐time monitoring of cell culture bioreactors , 2015, Biotechnology progress.

[23]  T. De Beer,et al.  Process analytical tools for monitoring, understanding, and control of pharmaceutical fluidized bed granulation: A review. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[24]  Gavin K Reynolds,et al.  The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[25]  Gabriele Reich,et al.  Combining microwave resonance technology to multivariate data analysis as a novel PAT tool to improve process understanding in fluid bed granulation. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[26]  Ana Casali,et al.  Particle size distribution soft-sensor for a grinding circuit , 1998 .

[27]  Éric Poulin,et al.  Nonlinear model predictive control of a batch fluidized bed dryer for pharmaceutical particles , 2017 .