Analysis of fluidized bed granulation process using conventional and novel modeling techniques.

Various modeling techniques have been applied to analyze fluidized-bed granulation process. Influence of various input parameters (product, inlet and outlet air temperature, consumption of liquid-binder, granulation liquid-binder spray rate, spray pressure, drying time) on granulation output properties (granule flow rate, granule size determined using light scattering method and sieve analysis, granules Hausner ratio, porosity and residual moisture) has been assessed. Both conventional and novel modeling techniques were used, such as screening test, multiple regression analysis, self-organizing maps, artificial neural networks, decision trees and rule induction. Diverse testing of developed models (internal and external validation) has been discussed. Good correlation has been obtained between the predicted and the experimental data. It has been shown that nonlinear methods based on artificial intelligence, such as neural networks, are far better in generalization and prediction in comparison to conventional methods. Possibility of usage of SOMs, decision trees and rule induction technique to monitor and optimize fluidized-bed granulation process has also been demonstrated. Obtained findings can serve as guidance to implementation of modeling techniques in fluidized-bed granulation process understanding and control.

[1]  L. Patel,et al.  INFLUENCE OF PROCESS VARIABLES ON PHYSICOCHEMICAL PROPERTIES OF THE GRANULATION MECHANISM OF DICLOFENAC SODIUM IN FLUID BED GRANULATION , 2010 .

[2]  Douglas M. Hawkins,et al.  The Problem of Overfitting , 2004, J. Chem. Inf. Model..

[3]  Step-up test with a single cutoff for unreplicated orthogonal designs , 2011 .

[4]  Brian Samas,et al.  An intravenous formulation decision tree for discovery compound formulation development. , 2003, International journal of pharmaceutics.

[5]  Teuvo Kohonen,et al.  Self-Organization and Associative Memory , 1988 .

[6]  Q Shao,et al.  Data mining of fractured experimental data using neurofuzzy logic-discovering and integrating knowledge hidden in multiple formulation databases for a fluid-bed granulation process. , 2008, Journal of pharmaceutical sciences.

[7]  Peter Wolschann,et al.  Validation of fluid bed granulation utilizing artificial neural network. , 2005, International journal of pharmaceutics.

[8]  K. Leiviskä,et al.  The advantages by the use of neural networks in modelling the fluidized bed granulation process , 1994 .

[9]  Sean Ekins,et al.  Application of data mining approaches to drug delivery. , 2006, Advanced drug delivery reviews.

[10]  Jukka Rantanen,et al.  Process analysis of fluidized bed granulation , 2008, AAPS PharmSciTech.

[11]  Jelena Parojčić,et al.  Artificial intelligence in pharmaceutical product formulation: Neural computing , 2009 .

[12]  Y. Roggo,et al.  A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies. , 2007, Journal of pharmaceutical and biomedical analysis.

[13]  José M. Aragón,et al.  Designing and Optimizing a Neural Network for the Modeling of a Fluidized-Bed Drying Process , 2002 .

[14]  Igor Skrjanc,et al.  Tableting process optimisation with the application of fuzzy models. , 2010, International journal of pharmaceutics.

[15]  Anil Menon,et al.  Identifying fluid-bed parameters affecting product variability , 1996 .

[16]  J. Ross Quinlan,et al.  C4.5: Programs for Machine Learning , 1992 .

[17]  J. Karl Hedrick,et al.  Air-to-fuel ratio control of spark ignition engines using Gaussian network sliding control , 1998, IEEE Trans. Control. Syst. Technol..

[18]  J. Rantanen,et al.  Visualization of fluid-bed granulation with self-organizing maps. , 2001, Journal of pharmaceutical and biomedical analysis.

[19]  Xiaoyang Xia,et al.  Solubility Prediction by Recursive Partitioning , 2003, Pharmaceutical Research.

[20]  Petr Horacek,et al.  Capitalizing on Aggregate Data for Gaining Process Understanding––Effect of Raw Material, Environmental and Process Conditions on the Dissolution Rate of a Sustained Release Product , 2007, Journal of Pharmaceutical Innovation.

[21]  R. Lenth Quick and easy analysis of unreplicated factorials , 1989 .

[22]  Satoru Watano,et al.  Direct control of wet granulation processes by image processing system , 2001 .

[23]  Lawrence X. Yu,et al.  Scientific Considerations of Pharmaceutical Solid Polymorphism in Abbreviated New Drug Applications , 2003, Pharmaceutical Research.

[24]  Aboul Ella Hassanien,et al.  Foundations of Computational Intelligence - Volume 6: Data Mining , 2009, Foundations of Computational Intelligence.

[25]  James B. Ramsey,et al.  If Nonlinear Models Cannot Forecast, What Use Are They? , 1996 .

[26]  Peter Wolschann,et al.  Comparison between two types of Artificial Neural Networks used for validation of pharmaceutical processes , 2009 .

[27]  T. Närvänen Particle Size Determination during Fluid Bed Granulation : Tools for Enhanced Process Understanding , 2009 .

[28]  Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development , Manufacturing , and Quality Assurance , 2004 .

[29]  William W. Cohen Fast Effective Rule Induction , 1995, ICML.

[30]  Jouko Yliruusi,et al.  Novel description of a design space for fluidised bed granulation. , 2007, International journal of pharmaceutics.

[31]  Svetlana Ibrić,et al.  The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit RS PO as matrix substance. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[32]  A Philip Plumb,et al.  A decision-support tool for the formulation of orally active, poorly soluble compounds. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[33]  Leo Breiman,et al.  Classification and Regression Trees , 1984 .

[34]  Michael Y. Hu,et al.  Forecasting with artificial neural networks: The state of the art , 1997 .

[35]  Q Shao,et al.  Comparison of neurofuzzy logic and decision trees in discovering knowledge from experimental data of an immediate release tablet formulation. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[36]  B. Chandra,et al.  Moving towards efficient decision tree construction , 2009, Inf. Sci..

[37]  J. Doucet,et al.  QSAR models for 2-amino-6-arylsulfonylbenzonitriles and congeners HIV-1 reverse transcriptase inhibitors based on linear and nonlinear regression methods. , 2009, European journal of medicinal chemistry.

[38]  M. Sherry Ku,et al.  Use of the Biopharmaceutical Classification System in Early Drug Development , 2008, The AAPS Journal.

[39]  R. Rowe,et al.  Novel approaches to neural and evolutionary computing in pharmaceutical formulation: challenges and new possibilities. , 2009, Future medicinal chemistry.