Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties.

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.