WEST LAFAYETTE, Ind., Nov. 9, 2023 /PRNewswire-PRWeb/ — Amorphous drugs have become a critical component in modern medicine and in drug development pipelines. Understanding the structural basis of phase stability of these materials is critical in the design of drug products, and yet remains a challenge due to the limited availability of high-resolution analytical tools. In early 2019, Dr. Allen Templeton of Merck & Co. and Dr. Stephen Byrn of Purdue University initiated a scientific project that proposed using synchrotron X-ray pair distribution function (SXPDF) and solid-state nuclear magnetic resonance (ssNMR) techniques to investigate amorphous pharmaceutical solids. Since then, scientists from Merck, Purdue, Argonne National Laboratory, and Improved Pharma have been collaborating on a research project involving the structure of amorphous posaconazole (POSA) and amorphous solid dispersions (ASDs) with hydroxypropyl methylcellulose acetate succinate (HPMCAS-L). Their work is described in the latest issue of Molecular Pharmaceutics.
Using SXPDF, ssNMR, and empirical potential structure refinement (EPSR), the team was able to successfully investigate the molecular structure of amorphous POSA in both its pure form and within polymeric matrices. The results from SXPDF and ssNMR agreed with each other and supported the determination of the short- and medium-range orders within the systems. The EPSR method provided a three-dimensional model of the packing arrangement in pure amorphous POSA. Combining the learnings from all three techniques, amorphous POSA was revealed to exhibit a rigid molecular conformation in both the crystalline and amorphous states, and neighboring POSA molecules were found to exist in a head-to-tail arrangement.
Moving forward, the researchers believe that combining these powerful techniques allows not only for an understanding of atomic structures but opens the door for investigating how different ASDs can be fine-tuned to provide different properties.
About Improved Pharma
Improved Pharma is a research and information company dedicated to improving pharmaceutical methods, formulations, and processes. Services include solid-state form studies, formulation design, synchrotron techniques, analytical testing, and expert consulting for the development and defense of intellectual property matters. The company was founded in 2006 by Stephen and Sarah Byrn, who also founded SSCI.