When drugmakers design and test dosage formulations of new medications, they mix hundreds of kilograms of the active pharmaceutical ingredient (API) with excipients such as polymer binders and inorganic salt lubricants to produce tablets. At this point in the drug development pipeline, time is short and supply of the API, which can cost thousands of dollars per kilogram, can become tight. To avoid losing time and money by synthesizing more drug, a Bristol-Myers Squibb development team has engineered a process to recover kilograms of pristine APIs from unused or off-spec tablets generated during formulation testing (Org. Process Res. Dev. 2017, DOI: 10.1021/acs.oprd.7b00146). Daniel S. Hsieh and co-workers first crush tablets containing the API, cellulose-based binders, magnesium stearate and silicon dioxide lubricants, and PVA-PEGpolymeric tablet coatings. After dissolving the material in warm water, the researchers separate out polymer and other solids by centrifuge, remove soluble polymers by ultrafiltration, and then remove water by reverse osmosis to concentrate the API. In the final step, they add acetone to precipitate out and recrystallise the API. This process, guided by theoretical modelling, is adjustable depending on the solubility, density, and other physical properties of the drug and the excipients. Overall, the Bristol-Myers Squibb approach recovers 90% of the API with better than 99% purity, which is sufficient for formulating new tablets and carrying out other studies. Hsieh and his colleagues consider the approach green engineering because its economical and minimises waste generation: No chemical steps are required, water is the separation medium, and mechanical energy rather than heat is the driving force for liquid separations using membranes.
Chemical & Engineering News, 31 July 2017 ; http://pubs.acs.org/cen/news