Crystallization and Solubility Studies Open access Peer reviewed

Microgravity Crystallization of Active Pharmaceutical Ingredients (APIs): Impact on Crystalline Forms

Kamryn Williams, Jessica Paulson, Miriam Garringer, Joanna Rajkumar and 6 more

Crystals | Oct 17, 2026

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It is demonstrated that microgravity can influence solid-form selectivity, phase purity, crystal habit, crystal size, and morphological uniformity to differing extents depending on the system.

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Controlling the nature of solid forms of active pharmaceutical ingredients (APIs) can enhance the chemical stability, increase or decrease the solubility, reduce the dose required, reduce waste production, increase manufacturing yield, and improve the route of therapeutic delivery. Mefenamic acid, theophylline, mebendazole, acetazolamide, and carbamazepine–saccharin cocrystals were crystallized in microgravity aboard the International Space Station and in matched ground controls, and were characterized by optical microscopy, Raman spectroscopy, and FTIR spectroscopy. The outcomes were system-dependent. Mebendazole and acetazolamide gave a single polymorph in flight, whereas the ground controls gave two-form mixtures. Mefenamic acid gave the anhydrous form in flight and the dimethylformamide solvate on the ground. The carbamazepine–saccharin cocrystal system gave cocrystal needles in the analyzed flight samples, whereas the ground control also contained free carbamazepine alongside the cocrystal, with no accompanying change in cocrystal form. Theophylline gave the same form in both environments, with the flight crystals more numerous, larger, and more uniform in size and appearance. This study demonstrates that microgravity can influence solid-form selectivity, phase purity, crystal habit, crystal size, and morphological uniformity to differing extents depending on the system.

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Kamryn Williams

first | Butler University

Jessica Paulson

middle | Butler University

Miriam Garringer

middle | Butler University

Joanna Rajkumar

middle | Butler University

Chloe Brecht

middle | Butler University

Carson Powers

middle | Butler University

Lillian Miller

middle | Butler University

Stephen Tuma

middle | SpaceX (United States)

Dom Hebrault

middle | SpaceX (United States)

Anne M. Wilson

last | Butler University | ORCID 0000-0003-0463-0280

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BibTeX

@article{Williams2026Microgravity,
  title = {Microgravity Crystallization of Active Pharmaceutical Ingredients (APIs): Impact on Crystalline Forms},
  author = {Kamryn Williams and Jessica Paulson and Miriam Garringer and Joanna Rajkumar and Chloe Brecht and Carson Powers and Lillian Miller and Stephen Tuma and Dom Hebrault and Anne M. Wilson},
  journal = {Crystals},
  year = {2026},
  doi = {10.3390/cryst16100669},
  url = {https://doi.org/10.3390/cryst16100669}
}

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