Printing of small molecular medicines from the vapor phase

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

doi:10.1038/s41467-017-00763-6

Title: Printing of small molecular medicines from the vapor phase

Journal Article · Wed Sep 27 00:00:00 EDT 2017 · Nature Communications

DOI:https://doi.org/10.1038/s41467-017-00763-6· OSTI ID:1422203

^[1];

^[1]; Mazzara, J. Maxwell ^[1]; Senabulya, Nancy ^[1]; Sinko, Patrick D. ^[1]; Fleck, Elyse ^[1]; Rockwell, Christopher ^[1]; Simopoulos, Nicholas ^[1]; Jones, Christina M. ^[1]; Schwendeman, Anna ^[1]; Mehta, Geeta ^[1]; Clarke, Roy ^[1]; Amidon, Gregory E. ^[1]; Shtein, Max ^[1]

Univ. of Michigan, Ann Arbor, MI (United States)

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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Univ. of Chicago, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences, and Biosciences Division

Grant/Contract Number:: FG02-94ER14466

OSTI ID:: 1422203

Journal Information:: Nature Communications, Vol. 8, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 12 works

Citation information provided by
Web of Science

References (47)

[p-(Diméthylamino-2 éthoxy)phényl]-1 trans-diphényl-1,2 butène-1 (tamoxfène) (ICI-46474) Precigoux, G.; Courseille, C.; Geoffre, S. Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, Vol. 35, Issue 12 https://doi.org/10.1107/S0567740879011407	journal	December 1979
Inkjet printing for pharmaceutics – A review of research and manufacturing Daly, Ronan; Harrington, Tomás S.; Martin, Graham D. International Journal of Pharmaceutics, Vol. 494, Issue 2 https://doi.org/10.1016/j.ijpharm.2015.03.017	journal	October 2015
On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system Adamo, A.; Beingessner, R. L.; Behnam, M. Science, Vol. 352, Issue 6281 https://doi.org/10.1126/science.aaf1337	journal	March 2016
Performance of single-photon-counting PILATUS detector modules Kraft, P.; Bergamaschi, A.; Broennimann, Ch. Journal of Synchrotron Radiation, Vol. 16, Issue 3 https://doi.org/10.1107/S0909049509009911	journal	April 2009
Comparison and Analysis of Theoretical Models for Diffusion-Controlled Dissolution Wang, Yanxing; Abrahamsson, Bertil; Lindfors, Lennart Molecular Pharmaceutics, Vol. 9, Issue 5 https://doi.org/10.1021/mp2002818	journal	April 2012
Tamoxifen: a most unlikely pioneering medicine Jordan, V. Craig Nature Reviews Drug Discovery, Vol. 2, Issue 3 https://doi.org/10.1038/nrd1031	journal	March 2003
Steady State Morphologies of Paracetamol Crystal from Different Solvents Li, Jinjin; Doherty, Michael F. Crystal Growth & Design, Vol. 17, Issue 2 https://doi.org/10.1021/acs.cgd.6b01510	journal	January 2017
Developing early formulations: Practice and perspective Li, Ping; Zhao, Luwei International Journal of Pharmaceutics, Vol. 341, Issue 1-2 https://doi.org/10.1016/j.ijpharm.2007.05.049	journal	August 2007
Transdermal Delivery of Drugs with Microneedles—Potential and Challenges Ita, Kevin Pharmaceutics, Vol. 7, Issue 3 https://doi.org/10.3390/pharmaceutics7030090	journal	June 2015
Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers Wolinsky, Jesse B.; Colson, Yolonda L.; Grinstaff, Mark W. Journal of Controlled Release, Vol. 159, Issue 1, p. 14-26 https://doi.org/10.1016/j.jconrel.2011.11.031	journal	April 2012
The Effect of Selected Water-Soluble Excipients on the Dissolution of Paracetamol and Ibuprofen Shaw, Lance R.; Irwin, William J.; Grattan, Tim J. Drug Development and Industrial Pharmacy, Vol. 31, Issue 6 https://doi.org/10.1080/03639040500215784	journal	January 2005
Angle calculations for a (2+3)-type diffractometer: focus on area detectors Schlepütz, Christian M.; Mariager, Simon O.; Pauli, Stephan A. Journal of Applied Crystallography, Vol. 44, Issue 1 https://doi.org/10.1107/S0021889810048922	journal	December 2010
Effect of crystal density on sublimation properties of molecular organic semiconductors Shalev, Olga; Shtein, Max Organic Electronics, Vol. 14, Issue 1, p. 94-99 https://doi.org/10.1016/j.orgel.2012.09.033	journal	January 2013
Solubilization and dissolution of tamoxifen‐hydroxybutenyl cyclodextrin complexes Buchanan, Charles M.; Buchanan, Norma L.; Edgar, Kevin J. Journal of Pharmaceutical Sciences, Vol. 95, Issue 10 https://doi.org/10.1002/jps.20710	journal	October 2006
End-to-End Continuous Manufacturing of Pharmaceuticals: Integrated Synthesis, Purification, and Final Dosage Formation Mascia, Salvatore; Heider, Patrick L.; Zhang, Haitao Angewandte Chemie International Edition, Vol. 52, Issue 47 https://doi.org/10.1002/anie.201305429	journal	October 2013
Direct, Mask- and Solvent-Free Printing of Molecular Organic Semiconductors Shtein, M.; Peumans, P.; Benziger, J. B. Advanced Materials, Vol. 16, Issue 18, p. 1615-1620 https://doi.org/10.1002/adma.200400260	journal	September 2004
The Crystal Structure of Anhydrous β-Caffeine as Determined from X-ray Powder-Diffraction Data Lehmann, Christian W.; Stowasser, Frank Chemistry - A European Journal, Vol. 13, Issue 10, p. 2908-2911 https://doi.org/10.1002/chem.200600973	journal	March 2007
Dependence of Reaction Velocity upon Surface and Agitation Hixson, A. W.; Crowell, J. H. Industrial & Engineering Chemistry, Vol. 23, Issue 10, p. 1160-1168 https://doi.org/10.1021/ie50262a025	journal	October 1931
The Rate Of Solution Of Solid Substances In Their Own Solutions Noyes, Arthur A.; Whitney, Willis R. Journal of the American Chemical Society, Vol. 19, Issue 12, p. 930-934 https://doi.org/10.1021/ja02086a003	journal	December 1897
Thin-Film Growth and Patterning Techniques for Small Molecular Organic Compounds Used in Optoelectronic Device Applications Biswas, Shaurjo; Shalev, Olga; Shtein, Max Annual Review of Chemical and Biomolecular Engineering, Vol. 4, Issue 1 https://doi.org/10.1146/annurev-chembioeng-061312-103356	journal	June 2013
Buccal bioadhesive drug delivery — A promising option for orally less efficient drugs Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A. K. Journal of Controlled Release, Vol. 114, Issue 1 https://doi.org/10.1016/j.jconrel.2006.04.012	journal	August 2006
The Structure of Two Anhydrous Polymorphs of Caffeine from Single-Crystal Diffraction and Ultrahigh-Field Solid-State ¹³ C NMR Spectroscopy Enright, Gary D.; Terskikh, Victor V.; Brouwer, Darren H. Crystal Growth & Design, Vol. 7, Issue 8 https://doi.org/10.1021/cg070291o	journal	August 2007
Solventless Pharmaceutical Coating Processes: A Review Bose, Sagarika; Bogner, Robin H. Pharmaceutical Development and Technology, Vol. 12, Issue 2 https://doi.org/10.1080/10837450701212479	journal	January 2007
Ab initio structure determination of the high-temperature phase of anhydrous caffeine by X-ray powder diffraction Derollez, Patrick; Correia, Natália T.; Danède, Florence Acta Crystallographica Section B Structural Science, Vol. 61, Issue 3 https://doi.org/10.1107/s010876810500546x	journal	May 2005
Advances in oral transmucosal drug delivery Patel, Viralkumar F.; Liu, Fang; Brown, Marc B. Journal of Controlled Release, Vol. 153, Issue 2 https://doi.org/10.1016/j.jconrel.2011.01.027	journal	July 2011
Improved data acquisition in grazing-incidence X-ray scattering experiments using a pixel detector Schlepütz, C. M.; Herger, R.; Willmott, P. R. Acta Crystallographica Section A Foundations of Crystallography, Vol. 61, Issue 4 https://doi.org/10.1107/S0108767305014790	journal	June 2005
Inkjet printing of drug substances and use of porous substrates‐towards individualized dosing Sandler, Niklas; Määttänen, Anni; Ihalainen, Petri Journal of Pharmaceutical Sciences, Vol. 100, Issue 8 https://doi.org/10.1002/jps.22526	journal	August 2011
Nanonization strategies for poorly water-soluble drugs Chen, Huabing; Khemtong, Chalermchai; Yang, Xiangliang Drug Discovery Today, Vol. 16, Issue 7-8, p. 354-360 https://doi.org/10.1016/j.drudis.2010.02.009	journal	April 2011
Solvent-free, direct printing of organic semiconductors in atmosphere Biswas, Shaurjo; Pipe, Kevin P.; Shtein, Max Applied Physics Letters, Vol. 96, Issue 26, Article No. 263301 https://doi.org/10.1063/1.3455840	journal	June 2010
“Higher density does not mean higher stability” mystery of paracetamol finally unraveled Nelyubina, Yulia V.; Glukhov, Ivan V.; Antipin, Mikhail Yu. Chemical Communications, Vol. 46, Issue 20 https://doi.org/10.1039/b927429d	journal	January 2010
The Prediction, Morphology, and Mechanical Properties of the Polymorphs of Paracetamol Beyer, Theresa; Day, Graeme M.; Price, Sarah L. Journal of the American Chemical Society, Vol. 123, Issue 21 https://doi.org/10.1021/ja0102787	journal	May 2001
Solvent Free Fabrication of Micro and Nanostructured Drug Coatings by Thermal Evaporation for Controlled Release and Increased Effects Zarie, Eman S.; Kaidas, Viktor; Gedamu, Dawit PLoS ONE, Vol. 7, Issue 8 https://doi.org/10.1371/journal.pone.0040746	journal	August 2012
Smart microneedle coatings for controlled delivery and biomedical analysis Khan, H.; Mehta, P.; Msallam, H. Journal of Drug Targeting, Vol. 22, Issue 9 https://doi.org/10.3109/1061186X.2014.921926	journal	June 2014
Comparative Solubilities in Water, in Pyridine and in Aqueous Pyridine. Dehn, William M. Journal of the American Chemical Society, Vol. 39, Issue 7 https://doi.org/10.1021/ja02252a012	journal	July 1917
Polymer strip films as a robust, surfactant-free platform for delivery of BCS Class II drug nanoparticles Krull, Scott M.; Susarla, Ramana; Afolabi, Afolawemi International Journal of Pharmaceutics, Vol. 489, Issue 1-2 https://doi.org/10.1016/j.ijpharm.2015.04.034	journal	July 2015
Growth and modelling of spherical crystalline morphologies of molecular materials Shalev, O.; Biswas, S.; Yang, Y. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6204	journal	October 2014
The phase transformation of caffeine: Investigation by dynamic X-ray diffraction and emanation thermal analysis Epple, M.; Cammenga, H. K.; Sarge, S. M. Thermochimica Acta, Vol. 250, Issue 1 https://doi.org/10.1016/0040-6031(94)01958-j	journal	February 1995
Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs Censi, Roberta; Di Martino, Piera Molecules, Vol. 20, Issue 10 https://doi.org/10.3390/molecules201018759	journal	October 2015
Physicochemical Hydrodynamics Levich, V. G.; Tobias, Charles W. Journal of The Electrochemical Society, Vol. 110, Issue 11 https://doi.org/10.1149/1.2425619	journal	January 1963
Coating Solid Dispersions on Microneedles via a Molten Dip‐Coating Method: Development and In Vitro Evaluation for Transdermal Delivery of a Water‐Insoluble Drug Ma, Yunzhe; Gill, Harvinder S. Journal of Pharmaceutical Sciences, Vol. 103, Issue 11 https://doi.org/10.1002/jps.24159	journal	November 2014
Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J. Journal of Pharmaceutical Sciences, Vol. 105, Issue 9 https://doi.org/10.1016/j.xphs.2015.10.008	journal	September 2016
An update on pharmaceutical film coating for drug delivery Felton, Linda A.; Porter, Stuart C. Expert Opinion on Drug Delivery, Vol. 10, Issue 4 https://doi.org/10.1517/17425247.2013.763792	journal	January 2013
Determination of Intrinsic Dissolution Rate Using Miniaturized Rotating and Stationary Disk Systems Tseng, Yin-Chao; Patel, Mita; Zhao, Youna Dissolution Technologies, Vol. 21, Issue 2 https://doi.org/10.14227/DT210214P24	journal	January 2014
Effect of pH on the structure and drug release profiles of layer-by-layer assembled films containing polyelectrolyte, micelles, and graphene oxide Han, Uiyoung; Seo, Younghye; Hong, Jinkee Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep24158	journal	April 2016
Advances in orodispersible films for drug delivery Hoffmann, Eva Maria; Breitenbach, Armin; Breitkreutz, Jörg Expert Opinion on Drug Delivery, Vol. 8, Issue 3, p. 299-316 https://doi.org/10.1517/17425247.2011.553217	journal	February 2011
Oral Mucosal Drug Delivery and Therapy Rathbone, Michael J.; Senel, Sevda; Pather, Indiran Advances in Delivery Science and Technology https://doi.org/10.1007/978-1-4899-7558-4	book	January 2015
Significance of controlling crystallization mechanisms and kinetics in pharmaceutical systems Rodríguez‐hornedo, Naír; Murphy, Denette Journal of Pharmaceutical Sciences, Vol. 88, Issue 7 https://doi.org/10.1021/js980490h	journal	July 1999

Cited By (2)

Organic Vapor-Jet Printing with Reduced Heat Transfer for Fabrication of Flexible Organic Devices Kim, Sungyeon; Moon, Hanul; Kwon, Hyukyun Advanced Materials Technologies, Vol. 4, Issue 2 https://doi.org/10.1002/admt.201800332	journal	October 2018
Addressing Unmet Clinical Needs with 3D Printing Technologies Ghosh, Udayan; Ning, Shen; Wang, Yuzhu Advanced Healthcare Materials, Vol. 7, Issue 17 https://doi.org/10.1002/adhm.201800417	journal	July 2018

Similar Records

Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

Journal Article · Tue Apr 01 00:00:00 EDT 2014 · Toxicology and Applied Pharmacology · OSTI ID:1422203

Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; +6 more

In-situ X-Ray Analysis of Rapid Thermal Processing for Thin-Film Solar Cells: Closing the Gap between Production and Laboratory Efficiency

Technical Report · Tue Feb 21 00:00:00 EST 2017 · OSTI ID:1422203

Toney, Michael F.; van Hest, Maikel F. A. M.

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

Journal Article · Thu Aug 10 00:00:00 EDT 2023 · Advanced Healthcare Materials · OSTI ID:1422203

Attia, Lucas; Chen, Liang‐Hsun; Doyle, Patrick S.

Related Subjects

60 APPLIED LIFE SCIENCES

Title: Printing of small molecular medicines from the vapor phase

Citation Formats

References (47)

Cited By (2)

Similar Records

Related Subjects