In a groundbreaking study, researchers have successfully demonstrated the feasibility of processing pharmaceuticals in microgravity environments. The team, led by scientists from Varda Space Industries and Improved Pharma LLC, crystallized the metastable Form III of ritonavir, an HIV protease inhibitor, in orbit and subsequently recovered the samples after reentry to Earth. This achievement paves the way for future in-space processing of medicines, enabling the development of novel drug products on Earth and supporting long-duration human exploration initiatives.
Experimental Design and Execution
The crystallization hardware, designed by Varda Space Industries, was housed within a compact, unmanned capsule capable of Earth reentry. The capsule was launched into orbit on a SpaceX Falcon 9 rocket on June 12th, 2023. In-orbit crystallization experiments were initiated on June 29th, 2023, with the melt temperature held at 131°C for 36 minutes, followed by a quench to the growth temperature of 80°C, which was maintained for nearly 24 hours before cooling to 15°C.
In addition to the three vials that underwent crystallization, four ritonavir control samples were placed in the capsule, thermally isolated from the crystallization hardware. These control vials contained amorphous ritonavir, Form I, Form II, and Form III, respectively, to determine if environmental factors experienced throughout the capsule’s lifetime influenced the final form of ritonavir.
Stability and Polymorphic Outcome
Upon retrieval of the capsule on February 21st, 2024, the crystallized and control samples were sent to the Improved Pharma facility for analysis. X-ray powder diffraction (XRPD) data and Raman spectra of the flight vials confirmed that all samples crystallized in microgravity were consistent with crystalline Form III. The control vials, which did not undergo crystallization in microgravity, were found to be of the same crystal form as packed, without detectable amorphous background. This indicates that neither in-orbit radiation nor conditions upon reentry caused polymorph conversion of ritonavir or crystallization of the amorphous ritonavir.
Implications and Future Directions
The successful recovery of the metastable Form III of ritonavir generated in orbit demonstrates the feasibility of processing pharmaceuticals in microgravity. The results highlight the importance of careful considerations of crystallization kinetics and thermophysical properties of crystals and their melts, alongside ground-based studies, to inform process sensitivity to gravitational forces.
Future work will examine polymorphic outcomes in microgravity by investigating additional molecules and expanding the range of thermal profiles examined. By demonstrating stability, this work enables a path towards in-space processing of pharmaceuticals that not only enables the development of novel drug products for use on Earth but also contributes to the feasibility of long-duration human exploration initiatives.
