Abstract
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.
Highlights
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
Formulating medicines with nanoparticles is challenging, since homogeneity and stability are difficult to achieve due to particle agglomeration and changes in crystallinity[8], compromising batch-to-batch consistency and safety, for high-potency active pharmaceutical ingredients (APIs) (HPAPIs)
How does the evaporation process affect the chemistry, structure, and functionality of a drug compound? Will advantageous film and particle morphologies be obtained when the API is printed at useful thicknesses and onto biocompatible substrates? Here we address these questions and demonstrate how films of small molecular medicines can be made controllably by organic vapor jet printing (OVJP), obtaining simultaneously: crystalline deposits, enhanced dissolution kinetics and bioavailability, and precise dosages
Summary
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. 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. To overcome the challenges outlined above, we adapt a process originally developed to achieve continuous, solvent-free, large-scale, high-throughput, yet ultraprecise printing of small-molecular organic semiconductors: organic vapor jet printing (OVJP)[22]. It proceeds by thermally evaporating the substance (here, an API) into a stream of inert carrier gas (e.g., nitrogen), followed by jetting onto a substrate, where the API forms a film (Fig. 1a, b). OVJP23–25 is unlike traditional ink-jet printing in that it operates without liquid solvents, eschewing the need to pre-dissolve the API26, 27, in principle making it attractive for a
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