Effect of roll compaction on granule size distribution of microcrystalline cellulose–mannitol mixtures: computational intelligence modeling and parametric analysis

Directory of Open Access Journals (Sweden)

Kazemi P

2017-01-01

Full Text Available Pezhman Kazemi,1 Mohammad Hassan Khalid,1 Ana Pérez Gago,2 Peter Kleinebudde,2 Renata Jachowicz,1 Jakub Szlęk,1 Aleksander Mendyk1 1Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland; 2Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany Abstract: Dry granulation using roll compaction is a typical unit operation for producing solid dosage forms in the pharmaceutical industry. Dry granulation is commonly used if the powder mixture is sensitive to heat and moisture and has poor flow properties. The output of roll compaction is compacted ribbons that exhibit different properties based on the adjusted process parameters. These ribbons are then milled into granules and finally compressed into tablets. The properties of the ribbons directly affect the granule size distribution (GSD and the quality of final products; thus, it is imperative to study the effect of roll compaction process parameters on GSD. The understanding of how the roll compactor process parameters and material properties interact with each other will allow accurate control of the process, leading to the implementation of quality by design practices. Computational intelligence (CI methods have a great potential for being used within the scope of quality by design approach. The main objective of this study was to show how the computational intelligence techniques can be useful to predict the GSD by using different process conditions of roll compaction and material properties. Different techniques such as multiple linear regression, artificial neural networks, random forest, Cubist and k-nearest neighbors algorithm assisted by sevenfold cross-validation were used to present generalized models for the prediction of GSD based on roll compaction process setting and material properties. The normalized root-mean-squared error and the coefficient of

Computational intelligence models to predict porosity of tablets using minimum features

Directory of Open Access Journals (Sweden)

Khalid MH

2017-01-01

Full Text Available Mohammad Hassan Khalid,1 Pezhman Kazemi,1 Lucia Perez-Gandarillas,2 Abderrahim Michrafy,2 Jakub Szlęk,1 Renata Jachowicz,1 Aleksander Mendyk1 1Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland; 2Centre National de la Recherche Scientifique, Centre RAPSODEE, Mines Albi, Université de Toulouse, Albi, France Abstract: The effects of different formulations and manufacturing process conditions on the physical properties of a solid dosage form are of importance to the pharmaceutical industry. It is vital to have in-depth understanding of the material properties and governing parameters of its processes in response to different formulations. Understanding the mentioned aspects will allow tighter control of the process, leading to implementation of quality-by-design (QbD practices. Computational intelligence (CI offers an opportunity to create empirical models that can be used to describe the system and predict future outcomes in silico. CI models can help explore the behavior of input parameters, unlocking deeper understanding of the system. This research endeavor presents CI models to predict the porosity of tablets created by roll-compacted binary mixtures, which were milled and compacted under systematically varying conditions. CI models were created using tree-based methods, artificial neural networks (ANNs, and symbolic regression trained on an experimental data set and screened using root-mean-square error (RMSE scores. The experimental data were composed of proportion of microcrystalline cellulose (MCC (in percentage, granule size fraction (in micrometers, and die compaction force (in kilonewtons as inputs and porosity as an output. The resulting models show impressive generalization ability, with ANNs (normalized root-mean-square error [NRMSE] =1% and symbolic regression (NRMSE =4% as the best-performing methods, also exhibiting reliable predictive