Vyazovkin Sergey, Dranca Ion
Department of Chemistry, University of Alabama at Birmingham, 901 S. 14th Street, Birmingham, AL 35294, USA.
Pharm Res. 2006 Sep;23(9):2158-64. doi: 10.1007/s11095-006-9050-1. Epub 2006 Aug 9.
To demonstrate the utility of differential scanning calorimetry (DSC) for determining activation energy landscape in amorphous pharmaceutical systems throughout the sub-Tg and Tg regions.
DSC was employed to determine the effective activation energies (E) of the relaxation in sub-Tg and Tg regions as well as the sizes of cooperatively rearranging regions in glassy maltitol and glucose.
It has been found that in the sub-Tg region E decreases with decreasing T reaching the values approximately 60 (glucose) and approximately 70 (maltitol) kJ mol(-1) that are comparable to the literature values of the activation energies for the beta-relaxation. In the Tg region E decreases (from approximately 250 to approximately 150 kJ mol(-1) in maltitol and from approximately 220 to approximately 170 kJ mol(-1) in glucose) with increasing T as typically found for the alpha-relaxation. From the heat capacity measurements the sizes of cooperatively rearranging regions have been determined as 3.1 (maltitol) and 3.3 (glucose) nm.
DSC can be used for evaluating the energy landscapes. The E values for maltitol are somewhat greater than for glucose due to the added impeding effect of the bulky substitute group in maltitol. The comparable sizes of the cooperatively rearranging regions suggest a similarity of the heterogeneous glassy structures of the two compounds.
证明差示扫描量热法(DSC)在确定非晶态药物体系在低于玻璃化转变温度(Tg)和Tg区域的活化能分布方面的实用性。
采用DSC测定玻璃态麦芽糖醇和葡萄糖在低于Tg和Tg区域弛豫的有效活化能(E)以及协同重排区域的大小。
发现在低于Tg区域,E随着温度降低而减小,达到约60(葡萄糖)和约70(麦芽糖醇)kJ·mol⁻¹的值,这与β弛豫活化能的文献值相当。在Tg区域,E随着温度升高而降低(麦芽糖醇中从约250降至约150 kJ·mol⁻¹,葡萄糖中从约220降至约170 kJ·mol⁻¹),这是α弛豫的典型特征。通过热容测量,协同重排区域的大小确定为3.1(麦芽糖醇)和3.3(葡萄糖)nm。
DSC可用于评估能量分布。由于麦芽糖醇中庞大取代基的附加阻碍作用,麦芽糖醇的E值比葡萄糖略大。协同重排区域大小相当表明这两种化合物的非均相玻璃态结构相似。