teriparatide (Xinfutai Pro)

Stability of Medicinal Nanoemulsions to Spaceflight: Insights From the StarMed Experiment.

Adebowale Modupe M, Long Nguyen Van Duc NVD, Williams Philip M PM, Hauslage Jens J et al.

Space missions require liquid drug formulations that remain physically stable and exhibit predictable release under launch, microgravity, and handling stresses. This study examined melatonin‑loaded nanoemulsions flown on the MAPHEUS‑15 sounding rocket, comparing an uncoated nanoemulsion (MN) with a chitosan‑coated nanoemulsion (CCN). Droplet size, polydispersity index (PDI), and zeta potential were measured at Day 0 and after spaceflight, ground vibration testing, matched ground controls, and laboratory storage. Melatonin release was quantified by dynamic dialysis and interpreted using a compartmental mass-transfer model. Melatonin‑loaded nanoemulsion (MN) showed a modest, systematic increase in droplet size under all post‑experiment conditions, with unchanged PDI and zeta potential, consistent with time‑dependent coalescence and Ostwald ripening rather than a specific microgravity effect. CCN maintained essentially unchanged droplet size, PDI, and zeta potential, indicating interfacial steric stabilization by chitosan. For MN, ageing and sounding‑rocket exposure increased the apparent fraction of melatonin available to the aqueous phase, but normalized release profiles overlapped when scaled to the fitted maximum releasable fraction, suggesting unchanged intrinsic release kinetics. In CCN, both the accessible fraction and the release profile were preserved. Overall, chitosan coating enhanced dimensional and release stability, supporting interfacial polymer coatings as a strategy for robust liquid pharmaceutical formulations for future space medicine.

Identification of related substances in baloxavir marboxil using 2D-LC-Q-TOF/MS.

Liu Zhi-Tong ZT, Ji Meng M, Yao Yan-Rong YR, Zuo Li-Juan LJ et al.

Baloxavir marboxil, a novel RNA polymerase inhibitor for the treatment of influenza, suppresses viral replication at the initiation stage of RNA transcription and has demonstrated significant clinical efficacy in reducing viral load and rapidly alleviating respiratory symptoms. Previous studies have primarily focused on its pharmacodynamics and clinical efficacy, whereas systematic investigations into its related substances (RSs) and their structural characteristics remain limited. In this study, two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS) was employed to detect and characterize process-related impurities in the baloxavir marboxil active pharmaceutical ingredient (API) and degradation products formed in its stressed samples, in accordance with the ICH Q1A(R2) guideline. Based on chromatographic retention behavior and high-resolution MS/MS fragmentation patterns, a total of 14 impurity-related peaks were characterized, including four process-related impurities and ten degradation products. Among them, six impurities, including IMP C and five degradation products (RSs 5, 6, 8, 9 and 12), were not found in the available literature and were characterized in this study. The major degradation pathways were proposed, involving side-chain hydrolysis, oxidation of the sulfur-containing aromatic ring, and the cleavage of heterocyclic linkages. Furthermore, a preliminary genotoxicity assessment of the characterized impurities was conducted in accordance with the ICH M7(R2) guideline using in-silico (Q)SAR prediction approaches, and revealed that these related substances did not exhibit genotoxic structural alerts. The determined impurity profile of baloxavir marboxil and the evaluated impurities' potential safety risks can provide a valuable reference for its impurity control, stability evaluation, and quality risk management.

A comparative study of the oxidative degradation of poloxamer 188, polysorbate 20 and polysorbate 80 in various buffered solutions.

Bollenbach Lukas L, Weber Johanna J, Schultz-Fademrecht Torsten T, Mäder Karsten K et al.

The importance of biologics has increased over the last few decades. Since proteins in liquid formulations tend to form protein particles in response to external stress factors, surfactants are added to prevent this. Currently, polysorbates (PSs) 20 and 80 are mainly used for this purpose. However, alternatives are being investigated, as PSs have stability issues, primarily due to oxidative or enzymatic degradation. The alternative that is discussed most frequently and already used in commercial biologics is poloxamer 188 (P188). However, this triblock copolymer, which consists of a polyoxypropylene block flanked by polyoxyethylene units, may also degrade through oxidative processes. Surprisingly, there are no direct comparative stability studies for PSs and P188. Therefore, the present study compared the oxidative degradation profiles of PS20 and PS80 with those of P188 in various relevant buffer systems. To this end, the formulations were subjected to stress in the form of 50 ppb (approximately 0.9 µM) of Fe2+ and light in the visible range, in line with their exposure during pharmaceutical production. Samples that received neither an iron spike nor light served as controls. The solutions contained 0.4 mg∙mL-1 PS20, PS80, or P188, respectively. The surfactants were formulated in either a 25 mM acetate, citrate, or histidine buffer solution (all pH 5.5) or in pure water. Significant differences were observed between these buffers, with greater effects at higher temperatures. The stability of the surfactant depended greatly on the buffer and the applied stress. All surfactants exhibited high rates of oxidative degradation when formulated in acetate buffer or pure water. PSs demonstrated the highest overall stability in citrate buffer, while P188 remained most stable in histidine, as well as in citrate buffer. However, both PSs exhibited instability in the presence of iron and light in histidine buffer, a phenomenon not observed in P188.

Widefield En Face OCT Visualization of Subretinal Perfluorocarbon Liquid.

Ishida Yuichiro Y, Kamei Motohiro M, Tsuboi Kotaro K