Comparison of multi-linear regression, particle swarm optimization artificial neural networks and genetic programming in the development of mini-tablets

In the present study, the preparation of pharmaceutical mini-tablets was attempted in the framework of Quality by Design (QbD) context, by comparing traditionally used multi-linear regression (MLR), with artificially-intelligence based regression techniques (such as standard artificial neural networks (ANNs), particle swarm optimization (PSO) ANNs and genetic programming (GP)) during Design of Experiment (DoE) implementation. Specifically, the effect of diluent type and particle size fraction for three commonly used direct compression diluents (lactose, pregelatinized starch and dibasic calcium phosphate dihydrate, DCPD) blended with either hydrophilic or hydrophobic flowing aids was evaluated in terms of: a) powder blend properties (such as bulk (Y1) and tapped (Y-2) density, Carr's compressibility index (Y-3, CCI), Kawakita's compaction fitting parameters a (Y-4) and 1/b (Y-5)), and b) mini-tablet's properties (such as relative density (Y-6), average weight (Y-7) and weight variation (Y-8)). Results showed better flowing properties for pregelatinized starch and improved packing properties for lactose and DPCD. MLR analysis showed high goodness of fit for the Y-1, Y-2, Y-4, Y-6 and Y-8 with RMSE values of Y-1 = 0.028, Y-2 = 0.032, Y-4 = 0.019, Y-6 = 0.015 and Y-8 = 0.130; while for rest responses, high correlation was observed from both standard ANNs and GP. PSO-ANNs fitting was the only regression technique that was able to adequately fit all responses simultaneously (RMSE values of Y-1 = 0.026, Y-2 = 0.022, Y-3 = 0.025, Y-4 = 0.010, Y-5 = 0.063, Y-6 = 0.013, Y-7 = 0.064 and Y-8 = 0.104).