The Role of TG/DTA in the Initial Evaluation of the Solid State Forms for Pharmaceutical New Chemical Entities Part Ⅰ: Evaluation of Pure Forms

摘要

TG/DTA plays a central role in the strategy outlined for early evaluation of the solid staternforms available to pharmaceutical new che mical entities. At this early stage of development,rncompound and time are typically at a premium so a successful strategy requires making the bestrnpossible use of the materials and time available. In addition, because of time and compoundrnlimitations, the goal of a solid state investigation is focused upon early stage objectives ratherrnthan development of a complete understanding of all available solid state forms.rnWhen pure forms were available, TG/DTA in combination with light microscopy andrnpowder X-ray diffraction provided an initial assignment of the solid state using no more than 5rnmilligrams of sample. Verification of the solid state assignment and characterization of hydraterntype required no more than 10 additional milligrams of sample.rnExamples of the testing strategy are provided for a lattice type hydrate and for a channelrntype hydrate. These examples demonstrate the ability of this strategy to quickly identifyrndifferences between solid state forms if present and to identify apparent differences caused byrnthe presence of residual solvent or over-drying of the materials. The data provided will illustraternthe need to distinguish between hydrate types to support an aggressive progression timetable.