Prediction of Sticking Potential for Continuous Direct Compression

An increasing number of drugs in development are hydrophobic and considered as BCS class 2 compounds. In many cases these drugs require aggressive pre-processing to reduce particle size and accelerate the dissolution of these compounds. The reduction in particle size causes even more hydrophobic surfaces of the drug particles which magnifies sticking issues. Sticking occurs more frequently in direct compression as the drug is not embedded within a granulation matrix. Considering that the industry is growing the use of continuous direct compression (CDC), a fundamental understanding of the underlying mechanisms of sticking becomes even more important. Typically, sticking is not observed until later stages of development where any alterations in the formulation or manufacturing route causes a large penalty of change. This project aims to increase the understanding of the underlying sticking mechanisms enabling the early detection of sticking. This will be addressed by using complementary advanced characterisation techniques with a focus on understanding the impact of particle size (drug and diluent) [3] of various hydrophobic compounds and lubrication on sticking propensity. The project will deliver a workflow to identify sticking at an early stage in the development and reduce the risk of sticking in CDC.

Overview

Grant agreement 13800BFE-AF54-4923-8E2F-004CF314EC6B