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Title: Printing of small molecular medicines from the vapor phase

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. In conclusion, 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.

Authors:
ORCiD logo [1]; ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of Michigan, Ann Arbor, MI (United States)
Publication Date:
Research Org.:
Univ. of Chicago, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Chemical Sciences, Geosciences & Biosciences Division
OSTI Identifier:
1422203
Grant/Contract Number:
FG02-94ER14466
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Shalev, Olga, Raghavan, Shreya, Mazzara, J. Maxwell, Senabulya, Nancy, Sinko, Patrick D., Fleck, Elyse, Rockwell, Christopher, Simopoulos, Nicholas, Jones, Christina M., Schwendeman, Anna, Mehta, Geeta, Clarke, Roy, Amidon, Gregory E., and Shtein, Max. Printing of small molecular medicines from the vapor phase. United States: N. p., 2017. Web. doi:10.1038/s41467-017-00763-6.
Shalev, Olga, Raghavan, Shreya, Mazzara, J. Maxwell, Senabulya, Nancy, Sinko, Patrick D., Fleck, Elyse, Rockwell, Christopher, Simopoulos, Nicholas, Jones, Christina M., Schwendeman, Anna, Mehta, Geeta, Clarke, Roy, Amidon, Gregory E., & Shtein, Max. Printing of small molecular medicines from the vapor phase. United States. doi:10.1038/s41467-017-00763-6.
Shalev, Olga, Raghavan, Shreya, Mazzara, J. Maxwell, Senabulya, Nancy, Sinko, Patrick D., Fleck, Elyse, Rockwell, Christopher, Simopoulos, Nicholas, Jones, Christina M., Schwendeman, Anna, Mehta, Geeta, Clarke, Roy, Amidon, Gregory E., and Shtein, Max. Wed . "Printing of small molecular medicines from the vapor phase". United States. doi:10.1038/s41467-017-00763-6. https://www.osti.gov/servlets/purl/1422203.
@article{osti_1422203,
title = {Printing of small molecular medicines from the vapor phase},
author = {Shalev, Olga and Raghavan, Shreya and Mazzara, J. Maxwell and Senabulya, Nancy and Sinko, Patrick D. and Fleck, Elyse and Rockwell, Christopher and Simopoulos, Nicholas and Jones, Christina M. and Schwendeman, Anna and Mehta, Geeta and Clarke, Roy and Amidon, Gregory E. and Shtein, Max},
abstractNote = {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. In conclusion, 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.},
doi = {10.1038/s41467-017-00763-6},
journal = {Nature Communications},
number = 1,
volume = 8,
place = {United States},
year = {Wed Sep 27 00:00:00 EDT 2017},
month = {Wed Sep 27 00:00:00 EDT 2017}
}

Journal Article:
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