A publication in Green Chemistry

Miniaturized production of a useful pharmaceutical for NASA space missions

Researchers from CiTOS - Center for Integrated Technology and Organic Synthesis (MolSys Research Unit) have developed a miniaturized production unit toward the first continuous flow synthesis of the anti-narcoleptic modafinil, one of the select medications available in the medical kit aboard the International Space Station (ISS). This project is being developed in collaboration with Crystallization Design Institute (CDI) of the University of Puerto Rico, within the frame of a NASA-EPSCoR program. This research is now published in the journal Green Chemistry and is highlighted as one the most impactful advancements in 2022 (2022 Green Chemistry Hot Articles).


odafinil, a wake-up agent and alleged cognitive enhancer (“smart drug”),  has itself awaken the interest of researchers due to its lack of addiction liabilities. Although originally approved to treat narcolepsy, its use has expanded to treat other energy-depriving conditions such as cancer or depression. Its unique profile has also made it into the only currently approved military stimulant go-pill and one of the select medications available in the medical kit aboard the International Space Station.

With a longstanding expertise in the field of continuous flow manufacturing of high added-value compounds, a miniaturized flow process allowing the production of modafinil was developed by researchers of the CiTOS laboratory (Center for Integrated Technology and Organic Synthesis), led by Jean-Christophe Monbaliu. Not only has the synthesis of modafinil been translated into a continuous flow procedure for the first time; it has also resulted in the most rapid, environmentally friendly, and inexpensive synthesis of modafinil reported to date. “This has been accomplished by harnessing the strengths of flow chemistry, such as highly efficient mixing, control of reaction stoichiometry and the effective intensification of reactions explains Jean-Christophe Monbaliu. Continuous flow technology alone does not guarantee de facto a significant reduction overall environmental footprint of a process; the chemistry and conditions/additives to access modafinil have also been completely revisited. In this way, our laboratory has succeeded in preparing modafinil from cheap starting materials in high purity, with a full dose of the final compound obtained in under 10 minutes with a hand-sized reactor. Isolation of a pharmaceutical grade product (US Pharmacopeia standards) has also been considerably simplified to increase its attractiveness.”

modafinil Monbaliu

Intensified, continuous flow process for the miniaturized production of active pharmaceutical modafinil.

The project is a NASA-sponsored collaboration with the University of Puerto Rico and the Crystallization Design institute (CDI, link) led by Dr. Torsten Stelzer as part of the development of an end-to-end medication system for Deep Space missions.

The final goal is to build a system that is sufficiently compact and efficient to allow medications to be prepared directly out in space concludes Diana Silva, first author and lead postdoctoral researcher affiliated with CDI and CiTOS. This capacity for on-the-spot preparation of medications is essential to beat the short medication shelf-life when considering future long-term missions in space.” However, the technology developed will also help address issues such as drug shortages, supply chain disruption, access to medication in remote locations, and the production of orphan drugs on Earth.

Scientific reference

V. Silva-Brenes, N. Emmanuel, V. López Mejías, J. Duconge, C. Vlaar, T. Stelzer and J.-C. M. Monbaliu, Out-smarting smart drug modafinil through flow chemistry, Green Chemistry, 2022, 24, 2094-2103.


This work is supported by NASA EPSCoR (Personalized Medication System for Deep Space Missions, NASA grant 80NSSC19M0148), the University of Puerto Rico, the University of Liège and the F.R.S.-FNRS (Incentive grant for scientific research MIS F453020F, JCMM).


Diana Silva

Jean-Christophe Monbaliu

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