Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation

Effects of polymeric additive and ultrasound on the morphology of ropivacaine crystals. [Display omitted] •The needle-like ropivacaine was modified as block-like crystals by adding little PVP in the crystallization system.•In ultrasound-assisted crystallization, the particles of ropivacaine precipit...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Ultrasonics sonochemistry 2023-07, Vol.97, p.106475-106475, Article 106475
Hauptverfasser: Wang, Yan, Zhang, Huixiang, Cai, Lun, Xue, Fumin, Chen, Hui, Gong, Junbo, Du, Shichao
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Effects of polymeric additive and ultrasound on the morphology of ropivacaine crystals. [Display omitted] •The needle-like ropivacaine was modified as block-like crystals by adding little PVP in the crystallization system.•In ultrasound-assisted crystallization, the particles of ropivacaine precipitated at extended ultrasonic time exhibited plate-like crystals with shorter aspect ratio.•Combined using of polymeric additive and ultrasound led to rice-shaped crystals, which the average particle size was further decreased.•The mechanism for the morphological evolution of ropivacaine crystals assisted by PVP and ultrasound was proposed based on the experiments and molecular dynamics simulation. The objective of this research was to modify the crystal shape and size of poorly water-soluble drug ropivacaine, and to reveal the effects of polymeric additive and ultrasound on crystal nucleation and growth. Ropivacaine often grow as needle-like crystals extended along the a-axis and the shape was hardly controllable by altering solvent types and operating conditions for the crystallization process. We found that ropivacaine crystallized as block-like crystals when polyvinylpyrrolidone (PVP) was used. The control over crystal morphology by the additive was related to crystallization temperature, solute concentration, additive concentration, and molecular weight. SEM and AFM analyses were performed providing insights into crystal growth pattern and cavities on the surface induced by the polymeric additive. In ultrasound-assisted crystallization, the impacts of ultrasonic time, ultrasonic power, and additive concentration were investigated. The particles precipitated at extended ultrasonic time exhibited plate-like crystals with shorter aspect ratio. Combined use of polymeric additive and ultrasound led to rice-shaped crystals, which the average particle size was further decreased. The induction time measurement and single crystal growth experiments were carried out. The results suggested that PVP worked as strong nucleation and growth inhibitor. Molecular dynamics simulation was performed to explore the action mechanism of the polymer. The interaction energies between PVP and crystal faces were calculated, and mobility of the additive with different chain length in crystal-solution system was evaluated by mean square displacement. Based on the study, a possible mechanism for the morphological evolution of ropivacaine crystals assisted by PVP and ultrasound was propose
ISSN:1350-4177
1873-2828
DOI:10.1016/j.ultsonch.2023.106475