Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation
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 wa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Ultrasonics Sonochemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1350417723001876 |
| _version_ | 1797801756050063360 |
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| author | Yan Wang Huixiang Zhang Lun Cai Fumin Xue Hui Chen Junbo Gong Shichao Du |
| author_facet | Yan Wang Huixiang Zhang Lun Cai Fumin Xue Hui Chen Junbo Gong Shichao Du |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | 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 proposed. |
| first_indexed | 2024-03-13T04:55:19Z |
| format | Article |
| id | doaj.art-2531353bbec349bb98de727aff8a64ca |
| institution | Directory Open Access Journal |
| issn | 1350-4177 |
| language | English |
| last_indexed | 2024-03-13T04:55:19Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ultrasonics Sonochemistry |
| spelling | doaj.art-2531353bbec349bb98de727aff8a64ca2023-06-18T05:01:17ZengElsevierUltrasonics Sonochemistry1350-41772023-07-0197106475Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulationYan Wang0Huixiang Zhang1Lun Cai2Fumin Xue3Hui Chen4Junbo Gong5Shichao Du6School of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR ChinaSchool of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR ChinaSchool of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR ChinaSchool of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR ChinaSchool of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR ChinaSchool of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR China; School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR ChinaSchool of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR China; Corresponding author at: School of Pharmaceutical Sciences (Shandong Analysis and Testing Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR China.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 proposed.http://www.sciencedirect.com/science/article/pii/S1350417723001876RopivacaineCrystallizationAdditivesUltrasoundMolecular simulation |
| spellingShingle | Yan Wang Huixiang Zhang Lun Cai Fumin Xue Hui Chen Junbo Gong Shichao Du Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation Ultrasonics Sonochemistry Ropivacaine Crystallization Additives Ultrasound Molecular simulation |
| title | Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation |
| title_full | Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation |
| title_fullStr | Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation |
| title_full_unstemmed | Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation |
| title_short | Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation |
| title_sort | polymer mediated and ultrasound assisted crystallization of ropivacaine crystal growth and morphology modulation |
| topic | Ropivacaine Crystallization Additives Ultrasound Molecular simulation |
| url | http://www.sciencedirect.com/science/article/pii/S1350417723001876 |
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