Prediction of Sticking Potential for Continuous Direct Compression

越来越多的药物是疏水性的，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前处理以减小颗粒尺寸并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疏水，从而放大了粘连问题。由于药物没有嵌入颗粒基质中，因此在直接压片中更容易发生粘连。考虑到该行业越来越多地使用连续直接压缩(CDC)，从根本上理解粘连的基本机制变得更加重要。通常情况下，粘连直到开发的后期才会被观察到，在此阶段，配方或制造路线的任何变化都会导致巨大的变化惩罚。该项目旨在增加对粘连的潜在机制的了解，从而能够及早发现粘连。这将通过使用补充的高级表征技术来解决，重点是了解各种疏水化合物的颗粒大小(药物和稀释剂)[3]和润滑对粘连倾向的影响。该项目将提供一个工作流程，以在开发的早期阶段识别卡住，并降低在疾控中心卡住的风险。

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.