Nanomilling for bioavailability enhancement: New capabilities at Eurofins CDMO in North America

Dr. Praveen Saligram, Head of Formulations, PraveenSaligram@eurofins.com; Kevin Rosenthal, Business Head, KevinRosenthal@eurofins.com; Drug Product Operations, Eurofins CDMO Alphora Inc.

Drug discovery programmes around the world are seeing an increase in challenging lead candidates when it comes to aqueous solubility. It is widely reported that more than 90% of New Chemical Entities (NCEs) in the discovery pipeline are poorly water-soluble. Nanomilling by agitator bead mills is a versatile formulation technique for bioavailability enhancement and offers several advantages for formulators and process engineers alike. The process is relatively easy to scale-up after critical process parameters are defined, and the advantages of nanomilling include the ability to incorporate high active payloads, establishment of a continuous process during milling, and reproducibility of particle size distribution from batch-to-batch.

Nanomilling is a top-down approach towards the reduction of particle size to below the sub-micron range. Particle size reduction via nanomill is achieved by the sheer force generated during collisions between the suspended drug substance and the milling media within an enclosed chamber. The use of a wet milling media in the process increases particle surface area by several thousand fold, thereby enhancing the in vivo rate of solution, which leads to enhanced bioavailability of an otherwise insoluble drug substance.

Along with the nanomilling capability, Eurofins CDMO Alphora has also acquired a Zetasizer analyser that allows for sub-micron particle size and surface charge measurement. This new technology provides an ability to develop and characterise sub-micron suspensions and other colloidal dispersion systems at the North American CDMO site. Coupled with these newer capabilities are the existing bioavailability enhancement techniques of micronisation by jet milling and amorphous solid dispersion (ASD) by spray drying. This suite of advanced technologies now provides clients a full complement of formulation enabling options for poorly soluble compounds. For more information, visit: www.eurofins.com/cdmo