Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth
Salbutamol sulfate is a selective β2-receptor agonist used to treat asthma and chronic obstructive pulmonary disease. The crystals of salbutamol sulfate usually appear as needles with a relatively large aspect ratio, showing poor powder properties. In this study, spherical particles of salbutamol su...
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2025-07-01
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| author | Xinyue Qiu Hongcheng Li Yanni Du Xuan Chen Shichao Du Yan Wang Fumin Xue |
| author_facet | Xinyue Qiu Hongcheng Li Yanni Du Xuan Chen Shichao Du Yan Wang Fumin Xue |
| author_sort | Xinyue Qiu |
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| description | Salbutamol sulfate is a selective β2-receptor agonist used to treat asthma and chronic obstructive pulmonary disease. The crystals of salbutamol sulfate usually appear as needles with a relatively large aspect ratio, showing poor powder properties. In this study, spherical particles of salbutamol sulfate were obtained via antisolvent crystallization. Four different antisolvents, including ethanol, n-propanol, n-butanol, and sec-butanol, were selected, and their effects on crystal form and morphology were compared. Notably, a new solvate of salbutamol sulfate with sec-butanol has been obtained. The novel crystal form was characterized by single-crystal X-ray diffraction, revealing a 1:1 stoichiometric ratio between solvent and salbutamol sulfate in the crystal lattice. In addition, the effects of crystallization temperature, solute concentration, ratio of antisolvent to solvent, feeding rate, and stirring rate on the morphology of spherical particles were investigated in different antisolvents. We have found that crystals grown from the n-butanol–water system at optimal conditions (25 °C, antisolvent/solvent ratio of 9:1, and drug concentration of 0.2 g·mL<sup>−1</sup>) could be developed into compact and uniform spherulites. The morphological evolution process was also monitored, and the results indicated a spherulitic growth pattern, in which sheaves of plate-like crystals gradually branched into a fully developed spherulite. This work paves a feasible way to develop new crystal forms and prepare spherical particles of pharmaceuticals. |
| format | Article |
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| institution | DOAJ |
| issn | 2073-4352 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-dedd0c10b9514d4592df0595daa437ee2025-08-20T03:07:57ZengMDPI AGCrystals2073-43522025-07-0115765110.3390/cryst15070651Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic GrowthXinyue Qiu0Hongcheng Li1Yanni Du2Xuan Chen3Shichao Du4Yan Wang5Fumin Xue6School of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, ChinaShouguang Fukang Pharmaceutical Co., Ltd., Shouguang 262700, ChinaBeyond Environmental Engineering Technology Co., Ltd., Hangzhou 310012, ChinaSchool of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, ChinaSchool of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, ChinaSchool of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, ChinaSchool of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, ChinaSalbutamol sulfate is a selective β2-receptor agonist used to treat asthma and chronic obstructive pulmonary disease. The crystals of salbutamol sulfate usually appear as needles with a relatively large aspect ratio, showing poor powder properties. In this study, spherical particles of salbutamol sulfate were obtained via antisolvent crystallization. Four different antisolvents, including ethanol, n-propanol, n-butanol, and sec-butanol, were selected, and their effects on crystal form and morphology were compared. Notably, a new solvate of salbutamol sulfate with sec-butanol has been obtained. The novel crystal form was characterized by single-crystal X-ray diffraction, revealing a 1:1 stoichiometric ratio between solvent and salbutamol sulfate in the crystal lattice. In addition, the effects of crystallization temperature, solute concentration, ratio of antisolvent to solvent, feeding rate, and stirring rate on the morphology of spherical particles were investigated in different antisolvents. We have found that crystals grown from the n-butanol–water system at optimal conditions (25 °C, antisolvent/solvent ratio of 9:1, and drug concentration of 0.2 g·mL<sup>−1</sup>) could be developed into compact and uniform spherulites. The morphological evolution process was also monitored, and the results indicated a spherulitic growth pattern, in which sheaves of plate-like crystals gradually branched into a fully developed spherulite. This work paves a feasible way to develop new crystal forms and prepare spherical particles of pharmaceuticals.https://www.mdpi.com/2073-4352/15/7/651salbutamol sulfatespherical crystallizationcrystal morphologysolvate |
| spellingShingle | Xinyue Qiu Hongcheng Li Yanni Du Xuan Chen Shichao Du Yan Wang Fumin Xue Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth Crystals salbutamol sulfate spherical crystallization crystal morphology solvate |
| title | Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth |
| title_full | Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth |
| title_fullStr | Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth |
| title_full_unstemmed | Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth |
| title_short | Crystal Form Investigation and Morphology Control of Salbutamol Sulfate via Spherulitic Growth |
| title_sort | crystal form investigation and morphology control of salbutamol sulfate via spherulitic growth |
| topic | salbutamol sulfate spherical crystallization crystal morphology solvate |
| url | https://www.mdpi.com/2073-4352/15/7/651 |
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