Prediction of Sticking Potential for Continuous Direct Compression

越来越多正在开发的药物是疏水性的，被认为是BCS 2类化合物。在许多情况下，这些药物需要积极的预处理，以减少颗粒大小和加速这些化合物的溶解。颗粒尺寸的减小导致药物颗粒的疏水表面更加明显，从而放大了粘附问题。由于药物没有嵌入到肉芽基质中，在直接压缩中粘连更频繁地发生。考虑到该行业越来越多地使用连续直接压缩（CDC），对粘接机制的基本理解变得更加重要。通常，直到开发后期，配方或制造路线的任何改变都会导致很大的变化，才会观察到粘着。该项目旨在提高对潜在粘滞机制的理解，从而尽早发现粘滞。这将通过使用互补的先进表征技术来解决，重点是了解各种疏水化合物的粒径（药物和稀释剂）[3]和润滑对粘着倾向的影响。该项目将提供一个工作流程，以在开发的早期阶段识别粘滞，并降低粘滞在CDC中的风险。

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.