The World Health Organization (W.H.O.) has maintained a list of essential medicines since 1977 (1). This list contains the medications considered to be the most effective and of the utmost importance to the needs of worldwide healthcare systems. If new forms of these drugs can be created, they can be studied for potential stability and transportation purposes, as well as drug delivery mechanisms. There are strategies to try and improve the physicochemical properties including forming polymorphs, salts, cocrystals, and amorphous formulations. There are issues with these techniques, and a large one is that in most cases the crystal structures of these compounds remain unknown. A common reason for this gap in crystallographic knowledge is that many of the drugs don’t crystallize as single crystals, but as polycrystalline powders.
In this work, powder x-ray diffraction (PXRD) data was collected on a prominent member of the World Health Organization (W.H.O.) Model Essential Medicines list - sodium cefotaxime (NaCFX). Here, a new method of placing drugs into a different physical form has been documented. By controlling the ratio of hydrogen bond donor and acceptor solvents (and choice of solvent) to a drug, or even multiple drugs, a glass can be formed. This is hypothesized to be due to the sodium coordination sites. Sodium coordination sites allow for the solvent to not only link to the sodium, but also to the drug through the sodium. Not only has a single drug been placed into this glassy form, but many have been placed within the same glass. Ranging from dyes, other antibiotics, and imaging drugs, over 25 glasses have been made, one of which contains 10 drugs.
In this work the most robust form of the glass (the NaCFX - methanol form) is examined and characterized. There is also some preliminary work completed for the NaCFX - water form and the NaCFX - ethanol form. The future directions of this research include determining the local structure of the glass material through neutron diffraction data, determining the anti-bacterial/microbial properties of the glasses, and the material characteristics including brittleness and ability to withstand humidity.
Dr. Brian Zoltowski
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Lamberti, Claire, "Clear as Glass: Novel Antibiotic Glasses Vitrified from Solution" (2023). Chemistry Theses and Dissertations. 41.
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