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

摘要

TG/DTA plays a central role in the strategy outlined for early evaluation of the solid staternforms available to pharmaceutical new chemical entities. At this stage of development,rncompound and time are often 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 the solid state investigation at this stage focuses upon early stagernobjectives rather than development of a complete understanding of all available solid state forms.rnExamples of the test strategies developed in the authors' laboratory are provided.rnWhen mixed forms were present within individual samples, TG/DTA in combinationrnwith light microscopy and powder X-ray diffraction provided evidence that samples representedrnmixed solid state forms. The initial assessment was made using as little as 5 milligrams ofrnsample. Hygroscopicity challenges provided further proof for mixed forms. To make a definiternassignment of the solid state forms present, isolation of pure phases of the suspected individualrnforms was necessary.rnSuccess of the testing strategy is illustrated using an example of mixed salt stoichiometryrnand mixed hydration states. A hierarchy is suggested for efficient isolation efforts when arncomplex mixture of solid state samples is present. Use of this strategy demonstrates the ability ofrnTG/DTA in combination with XRPD and hygroscopicity studies to unequivocally identify solidrnstate forms within a complex mixture.