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Objective: Acoustic droplet vaporization (ADV) is the liquid-to-gas phase transition of perfluorocarbon (PFC) droplets to microbubbles upon ultrasound insonation. After ADV, gases dissolved in the surrounding fluid diffuse into microbubbles, enabling oxygen scavenging. Characterization of oxygen scavenging and transition efficiency (TE) in whole blood has so far been limited. In this work, oxygen scavenging and perfluorocarbon droplet TE in a saline buffer and whole bovine blood were evaluated using blood-gas analysis and flow cytometry., Methods: Oxygen scavenging from whole blood via ADV was determined using an in vitro flow phantom with droplets comprising a phospholipid shell and either a decafluorobutane (DFB) or a perfluoropentane (PFP) core. Fluorescent droplets were used to determine ADV TE in whole blood via flow cytometry. Finally, a mathematical model predicting oxygen scavenging from whole blood was developed based on the experimental TE values., Results: DFB droplets enabled greater oxygen scavenging and higher TE when compared with perfluoropentane droplets in both buffer and whole blood. Increasing the droplet concentration resulted in a greater amount of hemoglobin-bound and dissolved oxygen scavenging from whole blood. ADV of DFB droplets at a concentration of 5 × 10 -4 mL/mL yielded a total oxygen reduction of 913 μM. The TE decreased with increasing droplet concentration in both buffer and whole blood. Experimental oxygen scavenging data in whole blood aligned with the predicted values from the mathematical model., Conclusion: Increased oxygen scavenging and TE were achieved with DFB droplets relative to perfluoropentane droplets., Competing Interests: Conflict of Interest C.K.H. and K.J.H. have been consultants with Boston Scientific Inc. All other authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Long-acting crystal suspensions of active pharmaceutical ingredients (API) mostly comprised of an API, a suspension media (water) and excipients and provide sustained API release over time. Excipients are crucial for controlling particle size and to achieve the stability of the API crystals in suspension. A bottom-up process was designed to produce long-acting crystal suspensions whilst investigating the excipient requirements during the production process and the subsequent storage. PVP K30 emerged as the most effective excipient for generating stable naproxen crystals with the desired size of 1 to 15 μm, using ethanol as solvent and water as anti-solvent. Calculations, performed based on the crystal properties and assuming complete PVP K30 adsorption on the crystal surface, revealed lower PVP K30 requirements during storage compared to initial crystal generation. Consequently, a membrane-based diafiltration process was used to determine and fine-tune PVP K30 concentration in the suspension post-crystallization. A seven-stage diafiltration process removed 98 % of the PVP K30 present in the suspension thereby reducing the PVP-to-naproxen ratio from 1:2 to 1:39 without impacting the stability of naproxen crystals in suspension. This work provides insights into the excipient requirements at various production stages and introduce the membrane-based diafiltration for precise excipient control after crystallization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Given that impurities may affect the quality and safety of drug products, impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol, which is used to treat excessive daytime sleepiness. Although the high-performance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities, their synthesis, structure elucidation, and chromatographic determination have not been reported yet. To bridge this gap, we herein identified, synthesized, and isolated eight process-related solriamfetol impurities, characterized them using spectroscopic and chromatographic techniques, and proposed plausible mechanisms of their formation. Moreover, we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection, revealing that its selectivity, linearity, accuracy, precision, and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Thus, the developed method was concluded to be suitable for the routine analysis of solriamfetol substances., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Acoustic droplet vaporization is the ultrasound-mediated phase change of liquid droplets into gas microbubbles. Following the phase change, oxygen diffuses from the surrounding fluid into the microbubble. An in vitro model was used to study the effects of droplet diameter, the presence of an ultrasound contrast agent, ultrasound duty cycle, and droplet concentration on the magnitude of oxygen scavenging in oxygenated deionized water. Perfluoropentane droplets were manufactured through a microfluidic approach at nominal diameters of 1, 3, 5, 7, 9, and 12 µm and studied at concentrations varying from 5.1 × 10 -5 to 6.3 × 10 -3 mL/mL. Droplets were exposed to an ultrasound transduced by an EkoSonic TM catheter (2.35 MHz, 47 W, and duty cycles of 1.70%, 2.34%, or 3.79%). Oxygen scavenging and the total volume of perfluoropentane that phase-transitioned increased with droplet concentration. The ADV transition efficiency decreased with increasing droplet concentration. The increasing duty cycle resulted in statistically significant increases in oxygen scavenging for 1, 3, 5, and 7 µm droplets, although the increase was smaller than when the droplet diameter or concentration were increased. Under the ultrasound conditions tested, droplet diameter and concentration had the greatest impact on the amount of ADV and subsequent oxygen scavenging occurred, which should be considered when using ADV-mediated oxygen scavenging in therapeutic ultrasounds.