Application of Machine-Learning Algorithms for Better Understanding of Tableting Properties of Lactose Co-Processed with Lipid Excipients.

Jelena Djuris,Sandra Cvijic,Ivana Aleksic,Mihal Djuris,Svetlana Ibric,Slobodanka Cirin-Varadjan

doi:10.3390/pharmaceutics13050663

Abstract

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.

Highlights

Increase in the new forms of active pharmaceutical ingredients (APIs), in terms of their physicochemical and stability profiles, has put a great pressure to the selection of excipients with the appropriate functionalities
The presented results support further development and usage of co-processed excipients (CPEs) obtained by the melt-granulation procedure with the lipophilic glycerides
It has been demonstrated that CPE have superior properties compared to their physical mixture counterparts

Summary

Introduction

Increase in the new forms of active pharmaceutical ingredients (APIs), in terms of their physicochemical and stability profiles, has put a great pressure to the selection of excipients with the appropriate functionalities. In terms of large-scale manufacturing, co-processing (CP) of excipients has become a reliable option to facilitated formulation and manufacturing of variety of solid dosage forms for oral administration. CP provides superior properties to excipients, compared to the simple physical mixture of the components, and yet the absence of chemical changes ensures the safety of the novel excipients. The worldwide market of co-processed excipients (CPEs) is steadily growing and is expected to exceed. Development of directly compressible formulations with high doses of poorly flowing/compressible API remains a great challenge for the pharmaceutical industry [2]. Franc et al have reviewed benefits of CPEs for direct compression of tablets, especially in terms

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Conclusion