Artificial neural networks in tandem with molecular descriptors as predictive tools for continuous liposome manufacturing

Abstract

The current study utilized an artificial neural network (ANN) to generate computational models to achieve process optimization for a previously developed continuous liposome manufacturing system. The liposome formation was based on a continuous manufacturing system with a co-axial turbulent jet in a co-flow technology. The ethanol phase with lipids and aqueous phase resulted in liposomes of homogeneous sizes. The input features of the ANN included critical material attributes (CMAs) (e.g., hydrocarbon tail length, cholesterol percent, and buffer type) and critical process parameters (CPPs) (e.g., solvent temperature and flow rate), while the ANN outputs included critical quality attributes (CQAs) of liposomes (i.e., particle size and polydispersity index (PDI)). Two common ANN architectures, multiple-input-multiple-output (MIMO) models and multiple-input-single-output (MISO) models, were evaluated in this study, where the MISO outperformed MIMO with improved accuracy. Molecular descriptors, obtained from PaDEL-Descriptor software, were used to capture the physicochemical properties of the lipids and used in training of the ANN. The combination of CMAs, CPPs, and molecular descriptors as inputs to the MISO ANN model reduced the training and testing mean relative error. Additionally, a graphic user interface (GUI) was successfully developed to assist the end-user in performing interactive simulated risk analysis and visualizing model predictions.

Keywords: Artificial neural network (ANN); Co-axial turbulent jet flow; Graphical user interface (GUI); Liposomes; Molecular descriptors; Predictive modeling.