Co-processing (CP) provides superior properties to excipients and has become a reliable option to facilitated formulation and manufacturing of variety of solid dosage forms. Development of directly compressible formulations with high doses of poorly flowing/compressible active pharmaceutical ingredients, such as paracetamol, remains a great challenge for the pharmaceutical industry due to the lack of understanding of the interplay between the formulation properties, process of compaction, and stages of tablets' detachment and ejection. The aim of this study was to analyze the influence of the compression load, excipients' co-processing and the addition of paracetamol on the obtained tablets' tensile strength and the specific parameters of the tableting process, such as (net) compression work, elastic recovery, detachment, and ejection work, as well as the ejection force. Two types of neural networks were used to analyze the data: classification (Kohonen network) and regression networks (multilayer perceptron and radial basis function), to build prediction models and identify the variables that are predominantly affecting the tableting process and the obtained tablets' tensile strength. It has been demonstrated that sophisticated data-mining methods are necessary to interpret complex phenomena regarding the effect of co-processing on tableting properties of directly compressible excipients.
Keywords: co-processed excipients; compaction analysis; lactose; lipid excipients; machine learning; monohydrate; multilayer perceptron; neural networks; sensitivity analysis; tensile strength.