Pharmaceutical Chemistry Department, National Organization for Drug Control and Research, Pyramids Avenue, P.O. Box 29, Giza, Egypt.
J Anal Methods Chem. 2012;2012:439082. doi: 10.1155/2012/439082. Epub 2012 Jun 20.
The thermal behavior of some sulfone-containing drugs, namely, dapsone (DDS), dimethylsulfone (MSM), and topiramate (TOP) in drug substances, and products were investigated using different thermal techniques. These include thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). The thermogravimetric data allowed the determination of the kinetic parameters: activation energy (E(a)), frequency factor (A), and reaction order (n). The thermal degradation of dapsone and topiramate was followed a first-order kinetic behavior. The calculated data evidenced a zero-order kinetic for dimethylsulfone. The relative thermal stabilities of the studied drugs have been evaluated and follow the order DDS > TOP > MSM. The purity was determined using DSC for the studied compounds, in drug substances and products. The results were in agreement with the recommended pharmacopoeia and manufacturer methods. DSC curves obtained from the tablets suggest compatibility between the drugs, excipients and/or coformulated drugs. The fragmentation pathway of dapsone with mass spectrometry was taken as example, to correlate the thermal decomposition with the resulted MS-EI. The decomposition modes were investigated, and the possible fragmentation pathways were suggested by mass spectrometry.
采用多种热分析技术(热重分析(TGA)、微商热重分析(DTG)、差热分析(DTA)和差示扫描量热法(DSC))研究了一些含砜类药物(即氨苯砜(DDS)、二甲亚砜(MSM)和托吡酯(TOP))的药物原料和制剂的热行为。热重分析数据允许确定动力学参数:活化能(E(a))、频率因子(A)和反应级数(n)。DDS 和 TOP 的热降解遵循一级动力学行为。MSM 的计算数据表明其遵循零级动力学。研究药物的相对热稳定性按以下顺序排列:DDS > TOP > MSM。采用 DSC 法测定了研究化合物在原料药和制剂中的纯度。结果与推荐的药典和制造商方法一致。从片剂获得的 DSC 曲线表明药物、赋形剂和/或共制剂之间具有相容性。以质谱法研究 DDS 的断裂途径为例,将热分解与所得 MS-EI 相关联。通过质谱法研究了分解模式,并提出了可能的断裂途径。