Jain Amit Kumar, Panchagnula Ramesh
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, Phase-X, SAS Nagar, Mohali 160 062, Punjab, India.
Int J Pharm. 2003 Jan 2;250(1):287-93. doi: 10.1016/s0378-5173(02)00550-1.
The aim of this investigation was to study the effect of temperature on the permeation of imipramine hydrochloride (IMH) across rat skin from two different vehicles. Differential scanning calorimetry (DSC) was used to characterize the phase transitions of rat epidermis and extracted rat SC lipids, and the transition temperatures were correlated with the permeability of IMH at different temperatures. Permeability of IMH from ethanol and propylene glycol (PG) was determined at five different temperatures and observed that a significant increase in IMH permeability occurred 45 degrees C from both the vehicles. Further, high energies of activation for rat skin permeation suggested that IMH diffuses across intercellular lipid matrix and therefore any change in the packing of SC lipids will have an effect on IMH permeation. Three endotherms T(1), T(2) and T(3) of rat epidermis were observed in DSC thermograms at 44, 53 and 64 degrees C and were assigned as transitions corresponding to orthorhombic to hexagonal, hexagonal to more disordered phase and melting of lipids with high cholesterol content, respectively. The high permeability values of IMH above 45 degrees C were therefore reasoned to be because of orthorhombic to hexagonal phase transition in rat skin from close to that temperature.
本研究的目的是研究温度对盐酸丙咪嗪（IMH）从两种不同载体透过大鼠皮肤的影响。采用差示扫描量热法（DSC）表征大鼠表皮和提取的大鼠角质层（SC）脂质的相变，并将转变温度与不同温度下IMH的渗透性相关联。在五个不同温度下测定了IMH从乙醇和丙二醇（PG）中的渗透率，发现从两种载体中在45℃时IMH渗透率均显著增加。此外，大鼠皮肤渗透的高活化能表明IMH跨细胞间脂质基质扩散，因此SC脂质堆积的任何变化都会对IMH渗透产生影响。在DSC热谱图中观察到大鼠表皮有三个吸热峰T(1)、T(2)和T(3)，分别出现在44℃、53℃和64℃，并分别对应于正交晶系到六方晶系、六方晶系到更无序相以及高胆固醇含量脂质的熔化转变。因此，45℃以上IMH的高渗透率被认为是由于大鼠皮肤在接近该温度时发生了正交晶系到六方晶系的相变。
