Polymorphic Crystallization of Organic Molecules
Active pharmaceutical ingredients (APIs), frequently delivered to the patient in the solid-state as part of an approved dosage form, can exist in a variety of distinct solid forms, including polymorphs, pseudopolymorphs, salts, co-crystals and amorphous solids. Polymorphism may be defined as the ability of a compound to exist in different crystalline forms in which the molecules have different arrangements (packing polymorphism) and/or conformations (conformational polymorphism) in the crystal lattice. Various polymorphs often display different mechanical, thermal, physical and chemical properties that can profoundly influence the bioavailability, hygroscopicity, stability and other performance characteristics of the drug. Hence, a thorough understanding of the relationship between the particular polymorph of an active pharmaceutical ingredient (API) and its functional properties is important in selecting the most suitable polymorph of the active pharmaceutical ingredient (API) for development into a drug product. In past decades, there has been significant emphasis on the selection and characterization of the polymorphs of the active pharmaceutical ingredients (APIs) or bulk drug. Taking stavudine as a model API, this contribution discusses the fundamentals of its polymorphism. The effect of supersaturation, nucleation temperature, cooling rate and solvent on the polymorphic crystallization of stavudine has been studied. Supersaturation is found to be the predominant controlling factor for the occurrence of polymorphs. Furthermore, when 1-butanol is used as the solvent, apart from forms I and II, a new metastable form IV can crystallize out at a moderate supersaturation level. Finally all three polymorphs have been characterized by DSC, TGA, PXRD, IGC, etc as well.
Lu Jie
School of Chemical and Material Engineering, JiangNan University
国际会议
International Symposium on Crystal Engineering and Drug Delivery System 2009(2009晶体工程与药物传送系统国际会议)
天津
英文
57
2009-09-05（万方平台首次上网日期，不代表论文的发表时间）