Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method
Clopidogrel bisulfate (CLP) form-I crystals are irregular, rectangular-shaped crystals. Because of their poor compressibility, flowability and their strong surface tension, manufacturers apply spherical crystallization methods to produce CLP form-I spherical agglomerates with a uniform particle size...
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MDPI AG
2019-01-01
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| Series: | Crystals |
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| Online Access: | http://www.mdpi.com/2073-4352/9/1/53 |
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| author | Ji-Hun An Alice Nguvoko Kiyonga Eun Hee Lee Kiwon Jung |
| author_facet | Ji-Hun An Alice Nguvoko Kiyonga Eun Hee Lee Kiwon Jung |
| author_sort | Ji-Hun An |
| collection | DOAJ |
| description | Clopidogrel bisulfate (CLP) form-I crystals are irregular, rectangular-shaped crystals. Because of their poor compressibility, flowability and their strong surface tension, manufacturers apply spherical crystallization methods to produce CLP form-I spherical agglomerates with a uniform particle size distribution. Consequently, manufacturers primarily synthesize CLP form-I crystal salts utilizing very complex methods, which produces form-I spherical agglomerates by means of spherical crystallization. In this study, spherical crystals of CLP Form-I were directly prepared from CLP Form-II, the most stable polymorph at room temperature, by using ethanol as solvent and a mixture of isopropyl alcohol (IPA)/n-Hexane (Hex) as an anti-solvent. To provide systematic inputs for the development of spherical agglomerates of optimal morphology, size, particle size distribution (PSD), and polymorphic form, processing parameters such as anti-solvent type, a mixture of IPA/Hex, pure Hex, or pure acetone; stirring speeds of 500, 600, 700, or 800 rpm; and temperatures ranging from 25 to 40 °C were explored. The effects of these parameters on spherical crystallization and polymorphic form were studied in terms of supersaturation, a driving force for polymorphic transformation, and the crystallization solution. Notably, our method does not require a large volume of anti-solvent which is the main complication of conventional anti-solvent crystallization methods. |
| first_indexed | 2024-04-11T22:26:31Z |
| format | Article |
| id | doaj.art-5dd7d171608240d4bcb880d9eb7c2e1e |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-04-11T22:26:31Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-5dd7d171608240d4bcb880d9eb7c2e1e2022-12-22T03:59:38ZengMDPI AGCrystals2073-43522019-01-01915310.3390/cryst9010053cryst9010053Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization MethodJi-Hun An0Alice Nguvoko Kiyonga1Eun Hee Lee2Kiwon Jung3College of Pharmacy, CHA University, Sungnam 13844, KoreaCollege of Pharmacy, CHA University, Sungnam 13844, KoreaCollege of Pharmacy, Korea University, Sejong City 30019, KoreaCollege of Pharmacy, CHA University, Sungnam 13844, KoreaClopidogrel bisulfate (CLP) form-I crystals are irregular, rectangular-shaped crystals. Because of their poor compressibility, flowability and their strong surface tension, manufacturers apply spherical crystallization methods to produce CLP form-I spherical agglomerates with a uniform particle size distribution. Consequently, manufacturers primarily synthesize CLP form-I crystal salts utilizing very complex methods, which produces form-I spherical agglomerates by means of spherical crystallization. In this study, spherical crystals of CLP Form-I were directly prepared from CLP Form-II, the most stable polymorph at room temperature, by using ethanol as solvent and a mixture of isopropyl alcohol (IPA)/n-Hexane (Hex) as an anti-solvent. To provide systematic inputs for the development of spherical agglomerates of optimal morphology, size, particle size distribution (PSD), and polymorphic form, processing parameters such as anti-solvent type, a mixture of IPA/Hex, pure Hex, or pure acetone; stirring speeds of 500, 600, 700, or 800 rpm; and temperatures ranging from 25 to 40 °C were explored. The effects of these parameters on spherical crystallization and polymorphic form were studied in terms of supersaturation, a driving force for polymorphic transformation, and the crystallization solution. Notably, our method does not require a large volume of anti-solvent which is the main complication of conventional anti-solvent crystallization methods.http://www.mdpi.com/2073-4352/9/1/53polymorphsclopidogrel bisulfateanti-solvent crystallizationspherical agglomerate |
| spellingShingle | Ji-Hun An Alice Nguvoko Kiyonga Eun Hee Lee Kiwon Jung Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method Crystals polymorphs clopidogrel bisulfate anti-solvent crystallization spherical agglomerate |
| title | Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method |
| title_full | Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method |
| title_fullStr | Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method |
| title_full_unstemmed | Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method |
| title_short | Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method |
| title_sort | simple and efficient spherical crystallization of clopidogrel bisulfate form i via anti solvent crystallization method |
| topic | polymorphs clopidogrel bisulfate anti-solvent crystallization spherical agglomerate |
| url | http://www.mdpi.com/2073-4352/9/1/53 |
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