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Wei-Ping Pan - Techniques in Thermal Analysis

作者:
: Hyphenated Techniques, Thermal Analysis of the Surface, and Fast Rate Analysis
ISBN :
803156162
出版日期:
2010-08-19 00:00:00
语言:
国家地区:
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Journal of ASTM International, January 2005, Vol. 2, No. 1 Paper ID JAI12792 Available online at www.astm.orgNancy L. Redman-Furey,1 Michael L. Dicks,2 Jane Godlweski,2 Dana C. Vaughn,3 and Wendy J. Collins3The Role of TGA-DTA in the Initial Evaluation of the Solid State Forms for Pharmaceutical New Chemical Entities, Part 2: Evaluation of Mixed FormsABSTRACT: TGA-DTA plays a central role in the strategy outlined for early evaluation of the solid state forms available to pharmaceutical new chemical entities. Understanding of the solid state forms becomes more difficult when individual samples present as mixed forms, especially when it is not immediately recognized that the samples represent a mixture. In this study, TGA-DTA, in combination with light microscopy and powder X-ray diffraction, provided immediate evidence that samples represented mixed solid state forms. The initial assessment was made using as little as 5 mg of sample. Hygroscopicity challenges provided further proof for mixed forms. To make a definite assignment of the solid state forms present, isolation of pure phases of the suspected individual forms was necessary. Success of this testing strategy is illustrated using an example of mixed salt stoichiometry and mixed hydration states. A hierarchy is suggested for efficient isolation efforts when a complex mixture of solid state samples is present. KEYWORDS: TGA, DTA, hydrate, thermal analysis, hygroscopicity, pharmaceutical, RisedronateIntroduction Early in the drug development process, supply of the New Chemical Entity (NCE) and time to characterize the NCE are often limited. In this environment, successful strategies focus upon rapidly obtaining as much information as possible from limited samples. Initial solid state studies often focus upon: identification of the form(s) in use, characterization of the properties of the form(s) in use, identification of any special handling or drying requirements, and monitoring for lot-to-lot differences in solid state form. Efforts to identify and characterize the solid state form become complicated when early drug lots present as mixed forms. Comprehensive reviews are available that discuss the need for solid state evaluation of pharmaceutical materials and describe the use of thermal analysis in the characterization of solvates and polymorphs [1,2]. The strategy developed in the authors' laboratory allows for lot-to-lot comparison using as little as 5 mg per lot, for initial assessment of phase purity and identity. Sequentially evaluating samples via microscopy, then x-ray powder diffraction (XRPD), and lastly thermogravimetry, combined with differential thermal analysis (TGA-DTA), ensures a visual record of a representative sample and conservation of sample by reuse of the XRPD sample, and it places the destructive test last in the sequence. When initial test results suggest the presence of mixed phases within a single sample, preparation of pure phases is required to confirm phase identity for each component. A logical sequence for preparation and evaluation of pure phases is suggested and illustrated.Manuscript received 24 May 2004; accepted for publication 15 September 2004; published January 2005. 1 Principal Scientist, P&G Pharmaceuticals, Inc., Norwich, New York, 13815. 2 Principal Researcher, P&G Pharmaceuticals, Inc., Norwich, New York, 13815. 3 Senior Researcher, P&G Pharmaceuticals, Inc., Norwich, New York 13815.Copyright 2005 by ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959.33
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