The application of machine learning algorithms in understanding the effect of core/shell technique on improving powder compactability

Graphical abstract Figure. No caption available. Abstract This study systemically investigated the application of core/shell technique to improve powder compactability. A 28‐run Design‐of‐Experiment (DoE) was conducted to evaluate the effects of the type of core and shell materials and their concentrations on tensile strength and brittleness index. Six machine learning algorithms were used to model the relationships of product profile outputs and raw material attribute inputs: response surface methodology (RSM), Support Vector Machine (SVM), and four different types of artificial neural networks (ANN), namely, Backpropagation Neural Network (BPNN), Genetic Algorithm Based BPNN (GA‐BPNN), Mind Evolutionary Algorithm Based BPNN (MEA‐BPNN), and Extreme Learning Machine (ELM). Their predictive and generalization performance were compared with the training dataset as well as an external dataset. The results indicated that the core/shell technique significantly improved powder compactability over the physical mixture. All machine learning algorithms being evaluated provided acceptable predictability and capability of generalization; furthermore, the ANN algorithms were shown to be more capable of handling convoluted and non‐linear patterns of dataset (i.e. the DoE dataset in this study). Using these models, the relationship of product profile outputs and raw material attribute inputs were disclosed and visualized.

[1]  Bernard F. Buxton,et al.  Drug Design by Machine Learning: Support Vector Machines for Pharmaceutical Data Analysis , 2001, Comput. Chem..

[2]  Changquan Calvin Sun,et al.  Tabletability Modulation Through Surface Engineering. , 2015, Journal of pharmaceutical sciences.

[3]  Demis Hassabis,et al.  Mastering the game of Go with deep neural networks and tree search , 2016, Nature.

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

[5]  Changquan Calvin Sun,et al.  A new tablet brittleness index. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  I. Larson,et al.  Effect of mechanical dry particle coating on the improvement of powder flowability for lactose monohydrate: A model cohesive pharmaceutical powder , 2011 .

[7]  Changquan Calvin Sun A classification system for tableting behaviors of binary powder mixtures , 2016 .

[8]  Hui Liu,et al.  New wind speed forecasting approaches using fast ensemble empirical model decomposition, genetic algorithm, Mind Evolutionary Algorithm and Artificial Neural Networks , 2015 .

[9]  Changquan Calvin Sun,et al.  Improving manufacturability of an ibuprofen powder blend by surface coating with silica nanoparticles , 2013 .

[10]  Changquan Calvin Sun,et al.  Dependence of tablet brittleness on tensile strength and porosity. , 2015, International journal of pharmaceutics.

[11]  Michael K. Gilson,et al.  Virtual Screening of Molecular Databases Using a Support Vector Machine , 2005, J. Chem. Inf. Model..

[12]  S. Agatonovic-Kustrin,et al.  Basic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research. , 2000, Journal of pharmaceutical and biomedical analysis.

[13]  Chee Kheong Siew,et al.  Extreme learning machine: Theory and applications , 2006, Neurocomputing.

[14]  Y. Kawashima,et al.  Effects of Granulation Method and Drug Dissolved in Binder Solution on Compressibility of Granules , 1990 .

[15]  Bruno C. Hancock,et al.  The influence of particle size on the surface roughness of pharmaceutical excipient compacts , 2005 .

[16]  Bernhard Schölkopf,et al.  A tutorial on support vector regression , 2004, Stat. Comput..

[17]  Kozo Takayama,et al.  Neural network based optimization of drug formulations. , 2003, Advanced drug delivery reviews.

[18]  Yixin Chen,et al.  Application of artificial neural networks in the design of controlled release drug delivery systems. , 2003, Advanced drug delivery reviews.

[19]  Hiroshi Ichikawa,et al.  Hierarchy neural networks as applied to pharmaceutical problems. , 2003, Advanced drug delivery reviews.

[20]  Changquan Calvin Sun,et al.  Improving Mechanical Properties of Caffeine and Methyl Gallate Crystals by Cocrystallization , 2008 .

[21]  Chongzhao Han,et al.  An extended mind evolutionary computation model for optimizations , 2007, Appl. Math. Comput..

[22]  Jens Sadowski,et al.  Comparison of Support Vector Machine and Artificial Neural Network Systems for Drug/Nondrug Classification , 2003, J. Chem. Inf. Comput. Sci..

[23]  R. Censi,et al.  Compression behaviour of anhydrous and hydrate forms of sodium naproxen. , 2010, International journal of pharmaceutics.

[24]  Changquan Calvin Sun,et al.  A top coating strategy with highly bonding polymers to enable direct tableting of multiple unit pellet system (MUPS) , 2017 .

[25]  C. Nyström,et al.  Assessing Tablet Bond Types from Structural Features that Affect Tablet Tensile Strength , 2001, Pharmaceutical Research.

[26]  Changquan Calvin Sun,et al.  Influence of Crystal Structure on the Tableting Properties of Sulfamerazine Polymorphs , 2001, Pharmaceutical Research.

[27]  Changquan Calvin Sun,et al.  Transforming powder mechanical properties by core/shell structure: compressible sand. , 2010, Journal of pharmaceutical sciences.

[28]  Bruno C. Hancock,et al.  Comparison of the mechanical properties of the crystalline and amorphous forms of a drug substance. , 2002, International journal of pharmaceutics.

[29]  Changquan Calvin Sun,et al.  Overcoming Poor Tabletability of Pharmaceutical Crystals by Surface Modification , 2011, Pharmaceutical Research.