(M1030-02-10) Drugs in Space: Evaluating the Effects of Drug-Product Package Changes in Drug Stability

Purpose: As missions to the Moon and Mars become more feasible, the effect on drug stability and efficacy has become a unique challenge, especially for longer missions. Additionally, space travel can place strict limits on cargo weight and rigidity, which can lead to the replacement of traditional drug product packaging with lighter-weight, albeit untested, storage containment. The inability to restock drugs that are fully consumed, or even degraded, further stresses how essential our understanding of drug packaging and stability can be to any space mission. The purpose of this study was to evaluate the impact of altering the packaging of drug products for space travel based on the assay, impurities and performance according to current methods used under the United State Pharmacopeia (USP).

Methods: Three drugs were evaluated from different classes: antibiotics (amoxicillin/clavulanate, 500mg/125mg tablet), hormone replacement (levothyroxine, 25 mcg tablet) and blocker/inhibitor (diltiazem, 60mg tablet). Each were chosen based on their susceptibility to degradation by hydrolysis and oxidation. Amoxicillin/clavulanate being highly sensitive followed by diltiazem and levothyroxine as being more stable, respectively. Each were stored under accelerated conditions (40°C/75%RH). Half in the original packaging (HDPE plastic bottles) and the other half in Ziplock bags currently used for space flight. The results were collected at time zero (T0), 2 months, 4 months and 6 months. Moisture content was also measured at each time point according to USP < 921 > by Karl Fischer. Tablet breaking force was evaluated at each time point according to USP < 1217 >.

Results: The appearance was not affected by the change in packaging for two of the evaluated drug products. The antibiotic (amoxicillin/clavulanate) did, however, show signs of degradation on the edges of the tablet. This visual sign of degradation was supported by a downward assay trend for both antibiotic drugs in Ziplock PE bags. Notably, the amoxicillin showed complete degradation within 2 months. The dissolution of the antibiotics was also impacted, but the observed changes were directly related to the changes in the assay–the rate of dissolution didn’t appear to change over time. Overall, the stability of diltiazem and levothyroxine were much less affected by the change in packaging. Other physical attributes were impacted by the change in packaging, such as the moisture, which appeared to change immediately and level out in the same amount of time. Lastly, the tablet breaking force was evaluated using USP < 1217 >, showing internal color change in some crushed tablets as well as significant hardening or softening of each set of drug tablets stored in Ziplock bags.

Conclusion: The change in packaging had an impact on the overall stability of all three drug products tested, some more significant than others, having a detrimental effect on the amoxicillin/clavulanate assay. The package change to Ziplock bags has shown to expose each active to environmental conditions, which has we found to also affect the tablet breaking points and some physical color. This study highlights the need for expanded stability testing for those drugs immediately used in space travel. Additionally, the development and testing of new, suitable packaging that meets the rigor of space travel while still protecting overall drug efficacy.

Acknowledgements: The author reports no conflict of interest. This research was conducted by Southwest Research Institute under SwRI project # 28572: "Accelerated Stability Analysis," final amended approval Jan 4, 2024. This work was performed in collaboration with NASA.

Figure 1. Appearance: Tablet comparison (a) Control, (b) Bottles (40°C/75%RH, 6 months), and (c) Ziplock PE Bags (40°C/75%RH, 6 months).

Figure 2. Stability (assay) of drugs exposed to accelerated conditions (40°C/75%RH) at varied time points.

Figure 3. Moisture content of drugs exposed to accelerated conditions (40°C/75%RH) at varied time points.