Application Note: Real-time quality prediction of continuously produced pharmaceutical granules

Continuous manufacturing approaches have been gaining interest in the pharmaceutical industry. They allow shorter production times, enable novel reaction pathways, increase assurances of product quality and help to realise cost savings…

Recent regulatory support of continuous manufacturing further encourages manufacturers to adapt new continuous approaches. A significant challenge posed by continuous manufacturing is an intensified need for real-time inline or online process monitoring. Offline sampling techniques are too slow to effectively monitor continuous processes. An ideal method for monitoring a continuous process would yield quantifiable information on specific chemical moieties quickly to enable real-time control of the process.

Granulation is a technique used to create solid dose tablets where API particles are bonded to excipient particles. Granules have several advantageous properties including better flow, less dust, higher density, and less segregation. Physical and chemical properties of the granules are crucial to their ability to be further processed into the final tablet product.

Important particle properties include flow, mechanical durability, porosity, size, and residual moisture content. Chemical and molecular structure properties of the active pharmaceutical ingredient (API) are also important, to ensure no process-induced transformations. Spectroscopic techniques are typically used to measure chemical and molecular structure API properties.

This note discusses an application of Raman spectroscopy for real-time, non-destructive evaluation of chemical changes in the API and solid-state properties of granules continuously produced.