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Ultrasound assisted crystallization of a new cardioactive prototype using ionic liquid as solvent

Abstract : This work deals with the antisolvent crystallization of LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) assisted by ultrasound. An ionic liquid (IL), 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] was used as solvent and water as antisolvent. The influence of the following parameters on crystals properties (size distribution, morphology, residual solvent and in vitro dissolution) were studied with two mixing mode (quick and dropwise) of solution with antisolvent. The impact of washing and drying process was also evaluated. Comparative studies of conventional crystallization conditions (without ultrasound) were also performed. The effect of ultrasound on LASSBio-294 recrystallized properties was influenced by the add mode, water/IL ratio and drug solution concentration. As example, US promoted the formation of small crystals with high residual IL under the following conditions: quick addition, high drug solution concentration and high water/IL ratio. However, despite the decrease of elementary particle size, ultrasound did not avoid crystals agglomeration. The drug dissolution rate was affected by the physical structure of agglomerates. When employed as drying process of washed crystals, spray drying reduced this agglomeration and improved the dissolution of LASSBio-294 crystals.
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Submitted on : Thursday, November 7, 2019 - 4:44:50 PM
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Jacqueline Resende de Azevedo, Fabienne Espitalier, Maria-Inês Ré. Ultrasound assisted crystallization of a new cardioactive prototype using ionic liquid as solvent. Ultrasonics Sonochemistry, 2019, 55, pp.32-43. ⟨10.1016/j.ultsonch.2019.03.011⟩. ⟨hal-02079415⟩



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