Kauffman John F, Batykefer Linda M, Tuschel David D
Food and Drug Administration, Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, 1114 Market Street, St. Louis, MO 63101, United States.
J Pharm Biomed Anal. 2008 Dec 15;48(5):1310-5. doi: 10.1016/j.jpba.2008.09.008. Epub 2008 Sep 11.
Acetaminophen is known to crystallize in three polymorphic forms. Thermally induced transformations between the crystalline forms and the super-cooled liquid have been observed by differential scanning calorimetry (DSC), but the assignment of calorimetric transitions to specific polymorphic transformations remains challenging, because the transition temperatures for several transformations are close to one another, and the characteristics of the observed transitions depend on experimental variables that are often poorly controlled. This paper demonstrates the simultaneous application of DSC and Raman microscopy for the observation of thermally driven transitions between polymorphs of pharmaceutical materials. Raman detected differential scanning calorimetry (RD-DSC) has been used to monitor the DSC thermograms of super-cooled liquid acetaminophen and confirms the assignment of two exothermic transitions to specific polymorphic transformations. Principal component analysis of the Raman spectra have been used to determine the number of independent components that participate in the phase transformations, and multivariate regression has been used to determine transition temperatures from the spectral data. The influence of the laser excitation source on measured DSC thermograms has also been investigated, and it has been demonstrated that a baseline shift occurs in RD-DSC when a polymorphic transformation occurs between crystalline and amorphous forms. RD-DSC has been used to examine the influence of sample aging and sample pan configuration on the observed polymorphic transformations, and both of these variables were found to influence the thermal behavior of the sample. The results demonstrate the advantage of simultaneous Raman spectroscopy and differential scanning calorimetry for the unambiguous assignment of thermally driven polymorphic transformations.
已知对乙酰氨基酚有三种多晶型形式会结晶。通过差示扫描量热法（DSC）观察到了晶体形式与过冷液体之间的热诱导转变，但将量热转变归属于特定的多晶型转变仍然具有挑战性，因为几种转变的转变温度彼此接近，而且观察到的转变特征取决于通常难以控制的实验变量。本文展示了同时应用DSC和拉曼显微镜来观察药物材料多晶型之间的热驱动转变。拉曼检测差示扫描量热法（RD-DSC）已用于监测过冷液体对乙酰氨基酚的DSC热谱图，并确认了两个放热转变归属于特定的多晶型转变。拉曼光谱的主成分分析已用于确定参与相变的独立成分数量，多元回归已用于从光谱数据确定转变温度。还研究了激光激发源对测量的DSC热谱图的影响，并且已证明当在晶体和非晶形式之间发生多晶型转变时，RD-DSC中会出现基线偏移。RD-DSC已用于研究样品老化和样品盘配置对观察到的多晶型转变的影响，并且发现这两个变量都会影响样品的热行为。结果证明了同时进行拉曼光谱和差示扫描量热法对于明确归属热驱动多晶型转变的优势。
