Degradation caused by incompatibility between sodium stearyl fumarate (PRUV) and AZD7986 in the drug product

Ludvigsson, Jufang Wu; Wikström, Håkan; Andersson, Thomas; Norrby, Per‐Ola

doi:10.1016/j.jpba.2018.05.036

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…DMT ( 2 ) fumarate, for example, has been previously used in clinical studies as an intravenous injection . Fumaric acid is, however, a known Michael acceptor and has been shown to form covalent products with amine-containing APIs under mild conditions. , Given that terminal sterilization by an autoclave may be required in the future preparation of sterile solutions of the 5-MeO-DMT drug product, the potential for this known reactivity with fumaric acid eliminated it as an acceptable salt form. Succinic acid is a structurally similar dicarboxylic acid but lacks the conjugated double bond present in fumaric acid and would not exhibit similar chemical reactivity.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use

Sherwood

Claveau

Lancelotta³

et al. 2020

ACS Omega

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To support clinical use, a multigram-scale process has been developed to provide 5-MeO-DMT, a psychedelic natural product found in the parotid gland secretions of the toad, Incilius alvarius. Several synthetic routes were initially explored, and the selected process featured an optimized Fischer indole reaction to 5-MeO-DMT freebase in high-yield, from which the 1:1 succinate salt was produced to provide 136 g of crystalline active pharmaceutical ingredient (API) with 99.86% peak area by highperformance liquid chromatography (HPLC) and a net yield of 49%. The report provides in-process monitoring, validated analytical methods, impurity formation and removal, and solidstate characterization of the API essential for subsequent clinical development.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use

Sherwood

Claveau

Lancelotta³

et al. 2020

ACS Omega

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“…Under the circumstance, it is feasible to improve the flame retardancy of TPU by exploiting fumarate organisms, which have little effect on the mechanical properties. Sodium fumarate (SF), as an important derivative of maleic anhydride and a by‐product in many chemical industries, has been applied in many fields such as chemistry and medicine, even as an additive in the food industry 30,31 . The special molecular structure of SF containing conjugated maleoyl and carbonyl groups endows SF with considerable thermal stability and chemical reactivity 32,33 .…”

Section: Introductionmentioning

confidence: 99%

Research on the fire safety effect of thermoplastic polyurethane elastomer based on sodium fumarate

Wei

Chen

Jiao

et al. 2021

Polymers for Advanced Techs

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Sodium fumarate (SF, C4H3NaO4), as a low‐cost and environment‐friendly additive, has been applied as the fire safety agent to investigate the flame retardancy and smoke suppression property in thermoplastic polyurethane elastomer (TPU). A series of tests were carried out, including limiting oxygen index (LOI), cone calorimeter test (CCT), smoke density test (SDT), and thermogravimetric/Fourier transform infrared spectroscopy (TG‐IR). The results proved that the addition of SF can significantly improve the fire safety property of TPU. Remarkably, in the case of the sample containing 2.0 wt% SF, LOI was raised up to 27.5 compared with 21.0 of pure TPU. The CCT results showed that pHRR, THR, TSR, and SF values decreased by 60.1%, 17.0%, 44.6%, and 66.4%, respectively, while the residual mass increased from 3.0% to 12.3% compared with pure TPU. The digital photographs displayed a more compact and intense carbon layer after the addition of SF. The SDT results indicated SF has increased the luminous flux and reduced Ds values, implying the improvement of the smoke suppression property of TPU. TG and TG‐IR results showed that the addition of SF has promoted the char forming process and reduced the release of CO2 and other volatile compounds. All results of tests illustrated that SF has considerable fire safety effect on TPU. Through the analysis of the results of this experiment, it will make a significance in the aspect of fire safety of polymer.

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