Exploring the complexities of drug formulation selection, storage, and shelf-life for exploration spaceflight.

Medications have been a part of space travel dating back to the Apollo missions. Currently, medical kits aboard the International Space Station (ISS) contain medications and supplies to treat a variety of possible medical events. As we prepare for more distant exploration missions to Mars and beyond, risk management planning for astronaut healthcare should include the assembly of a medication formulary that is comprehensive enough to prevent or treat anticipated medical events, remains safe and chemically stable, and retains sufficient potency to last for the duration of the mission. Emerging innovation and technologies in pharmaceutical development, delivery, quality maintenance, and validation offer promise for addressing these challenges. The present editorial will summarize the current state of knowledge regarding innovative formulary optimization strategies, pharmaceutical stability assessment techniques, and storage and packaging solutions that could enhance drug safety and efficacy for future exploration spaceflight missions.

Intranasal Scopolamine for Motion Sickness.

INTRODUCTION: Rapid onset, noninjection methods are required to provide "as needed" therapy for motion sickness. Intranasal scopolamine (IN SCOP) is attractive because it can be fast acting and work when gastric motility is slowed. Intranasal administration can provide a time to maximal concentration (Tmax) of drugs (e.g., naloxone and midazolam) of 30 min or less. We evaluated the efficacy, pharmacodynamics, and pharmacokinetics of IN SCOP in a placebo-controlled, randomized, double-blind, dose-ranging study, and compared pharmacokinetic outcomes against other published results.METHODS: There were 18 healthy adult volunteers (10 M, 8F) who received placebo, low dose (0.2 mg), and high dose (0.4 mg) IN SCOP intranasally using a pump device and a gel formulation. Participants rode in an off-vertical axis rotation (OVAR) chair 1.25 h after dose administration and completed neurocognitive tests to evaluate secondary drug impacts. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in eight subjects. PK data were compared to results from previously published studies.RESULTS: Low and high dose IN SCOP increased chair time significantly compared to placebo. No significant sleepiness or cognitive impairment was seen, likely due to the small sample size. Tmax was long for both dosages (High dose 75.0 ± 49.4 min, Low dose 61.9 ± 37.1 min), compared to other intranasally administered drugs and some previous studies with IN SCOP. Average Tmax was not superior to previously published values for dose-matched (0.4-0.5 mg), orally-delivered SCOP.DISCUSSION: IN SCOP has potential as a rapid administration route for relieving MS symptoms, but more work is needed to identify optimal intranasal formulation and dispensing methods.KEYWORDS: Motion sickness, pharmacokinetics, scopolamine, intranasal administration.Stankovic AS, Alvarenga DL, Daniels VRC, Simmons RG, Buckey JC, Putcha L. Intranasal scopolamine for motion sickness. Aerosp Med Hum Perform. 2019; 90(11):917-924.

Limitations in predicting radiation-induced pharmaceutical instability during long-duration spaceflight.

As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners face numerous challenges related to ensuring the safety of their astronauts, including the need to provide a safe and effective pharmacy for long-duration spaceflight. Historical missions have relied upon frequent resupply of onboard pharmaceuticals; as a result, there has been little study into the effects of long-term exposure of pharmaceuticals to the space environment. Of particular concern are the long-term effects of space radiation on drug stability, especially as missions venture away from the protective proximity of the Earth. Here we highlight the risk of space radiation to pharmaceuticals during exploration spaceflight, identifying the limitations of current understanding. We further seek to identify ways in which these limitations could be addressed through dedicated research efforts aimed toward the rapid development of an effective pharmacy for future spaceflight endeavors.

Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding.

In order to maintain crew health and performance during long-duration spaceflight outside of low-Earth orbit, NASA and its international partners must be capable of providing a safe and effective pharmacy. Given few directed studies of pharmaceuticals in the space environment, it is difficult to characterize pharmaceutical effectiveness or stability during spaceflight; this in turn makes it challenging to select an appropriate formulary for exploration. Here, we present the current state of literature regarding pharmaceutical stability, metabolism, and effectiveness during spaceflight. In particular, we have attempted to highlight the gaps in current knowledge and the difficulties in translating terrestrial-based drug studies to a meaningful interpretation of drug stability, safety, and effectiveness in space. We hope to identify high-yield opportunities for future research that might better define and mitigate pharmaceutical risk for exploration missions.

Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness.

Evaluation of physical and chemical changes in pharmaceuticals flown on space missions.

Efficacy and safety of medications used for the treatment of astronauts in space may be compromised by altered stability in space. We compared physical and chemical changes with time in 35 formulations contained in identical pharmaceutical kits stowed on the International Space Station (ISS) and on Earth. Active pharmaceutical content (API) was determined by ultra- and high-performance liquid chromatography after returning to Earth. After stowage for 28 months in space, six medications aboard the ISS and two of matching ground controls exhibited changes in physical variables; nine medications from the ISS and 17 from the ground met the United States Pharmacopeia (USP) acceptance criteria for API content after 28 months of storage. A higher percentage of medications from each flight kit had lower API content than the respective ground controls. The number of medications failing API requirement increased as a function of time in space, independent of expiration date. The rate of degradation was faster in space than on the ground for many of the medications, and most solid dosage forms met USP standard for dissolution after storage in space. Cumulative radiation dose was higher and increased with time in space, whereas temperature and humidity remained similar to those on the ground. Exposure to the chronic low dose of ionizing radiation aboard the spacecraft as well as repackaging of solid dosage forms in flight-specific dispensers may adversely affect stability of pharmaceuticals. Characterization of degradation profiles of unstable formulations and identification of chemical attributes of stability in space analog environments on Earth will facilitate development of space-hardy medications.