E!9231 Development of product for ultra fast PDF analysis of amorphous & nano pharmaceutical API compounds

Solid dosage oral forms are preferred formulation principles for the delivery of active pharmaceutical ingredients (APIs). They improve the patients adherence to the medication, address medical needs and patients centricity. During the last decades, the number of APIs exhibiting poor physical properties such as poor solubility of crystalline forms has increased. It may lead to poor in vivo efficacy, limited performance, and often requires to increase the doses that may lead to potentially side effects. Different formulations principles are then considered and may imply development of amorphous forms of APIs. An amorphous material can be substantially more soluble than the corresponding crystalline material, in some cases as much as 1600 times. However, amorphous forms may imply physical instability in the drug product, and potential re-crystallization of the engineered formulations. In order to mitigate these potential risks during pharmaceutical development and provide quality relevant specifications, advanced analytical technologies are required. To date, the current standard analytical tools and technologies are in most cases inappropriate to address the characterization of amorphous/nanocrystalline APIs. The objective of our project is high throughput characterization of amorphous and nanocrystalline pharmaceutical compounds combining a novel TEM pair distribution function technique (e-PDF) in combination with synchrotron x-ray powder diffraction (SR-XPRD)-PDF analysis. The project will lead to a dedicated software for e-PDF analysis and an adaptation of a novel direct detection detector to analyze beam sensitive pharmaceutical samples in TEM without using cooling holders. Benchmarking of the performance will be done with TEM samples of industrial interest to validate the e-PDF technique and build a PDF library. Our novel e- PDF technique will allow screening of amorphous/crystalline APIs samples with analysis times as short as a few seconds per sample

50% to 80% of promising pharma API candidates are abandoned due to poor acqueous solubility. An amorphous form of those API compounds can be as much as 1,600x more water soluble / bioavailable than the crystalline form. Therefore, when a reliable ultra fast e-PDF method for analysis of the amorphous API forms is developed and validated in our project, Pharma companies will be able to launch large-scale screening programs for these abandoned compounds leading to production of novel drugs. There is an expected need to analyze at least 14,000 amorphous and nano-crystalline samples in Europe, up to 16,000 samples in the USA and up to 14,000 in the RoW per year. Proposed novel e-PDF method will analyze amorphous pharmaceutical compounds 20x faster than current SoA methods. As the result of AMOURPHOUS_PHARMA project, BoRAS and Consortium Partners will (1) sell dedicated e-PDF software package with modified TEM detector unit (BoRAS and Partners) and (2) offer analytical services with TEM e-PDF in combination with Synchtrotron X-Ray PDF (Partners only, but BoRAS is expecting to receive Finders Fees for customer referrals). Customers will include (1) pharmaceutical companies that wish to analyze their drug leads in-house; (2) private contract research organizations (CROs) who work with TEM analysis of drug leads and (3) University laboratories that offer contract TEM services. We estimate that we would need around 6-12 months post-project to launch the commercial product and 3-6 months to launch the commercial service.