Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method
AbstractClopidogrel 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. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 209 KB)
Share & Cite This Article
An, J.-H.; Kiyonga, A.N.; Lee, E.H.; Jung, K. Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method. Crystals 2019, 9, 53.
An J-H, Kiyonga AN, Lee EH, Jung K. Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method. Crystals. 2019; 9(1):53.Chicago/Turabian Style
An, Ji-Hun; Kiyonga, Alice N.; Lee, Eun H.; Jung, Kiwon. 2019. "Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method." Crystals 9, no. 1: 53.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.