Printing of small molecular medicines from the vapor phase

Max Shtein

Professor

mshtein@umich.edu

3051W NCRC, Building 28

T: (734) 764-4312

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O Shalev, S Raghavan, M Mazzara, N Senabulya, PD Sinko, E Fleck, C Rockwell, N Simopoulos, CM Jones, A Schwendeman, G Mehta, R Clarke, GE Amidon, and M Shtein (2017)

NATURE COMMUNICATIONS, 8:711.

There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs. Here we demonstrate the use of solvent-free organic vapor jet printing to deposit nanostructured films of small molecular pharmaceutical ingredients, including caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein, with accuracy on the scale of micrograms per square centimeter, onto glass, Tegaderm, Listerine tabs, and stainless steel microneedles. The printed films exhibit similar crystallographic order and chemistry as the original powders; controlled, order-of-magnitude enhancements of dissolution rate are observed relative to powder-form particles. In vitro treatment of breast and ovarian cancer cell cultures in aqueous media by tamoxifen and BAY 11-7082 films shows similar behavior to drugs pre-dissolved in dimethyl sulfoxide. The demonstrated precise printing of medicines as films, without the use of solvents, can accelerate drug screening and enable continuous manufacturing, while enhancing dosage accuracy.

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