Ghaderi Faranak, Nemati Mahboob, Siahi-Shadbad Mohammad Reza, Valizadeh Hadi, Monajjemzadeh Farnaz
Department of Pharmaceutical and Food Control, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Food and Drug Safety Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2019 Jun;9(2):289-293. doi: 10.15171/apb.2019.033. Epub 2019 Jun 1.
Evaluation of drug-excipients compatibility is an important stage during preformulation studies. In the present research, differential scanning calorimetry (DSC) at different heating rates (2.5, 10, 15°C/min) was applied for the kinetic evaluation of fluvoxamine (FLM), sertraline (SER) and doxepin (DOX) binary mixtures with lactose. Solid state kinetic parameters of the mixtures were calculated using two different thermal methods including ASTM E698 and Starink and the effect of amine type (pKa value) was investigated based on the calculated activation energies. Based on obtained results mean activation energy calculated for FLM, SER and DOX with lactose using ASTM E698 and Starink methods are equal to 335.23, 132.02 and 270.99 kJ/ mol respectively. Results showed that the probability of drug-lactose interaction is higher in the SERlactose mixture in comparison with other two antidepressant drugs which is consistent with their pKa values.
药物辅料相容性评估是处方前研究中的一个重要阶段。在本研究中，采用不同升温速率（2.5、10、15℃/分钟）的差示扫描量热法（DSC）对氟伏沙明（FLM）、舍曲林（SER）和多塞平（DOX）与乳糖的二元混合物进行动力学评估。使用包括ASTM E698和Starink在内的两种不同热方法计算混合物的固态动力学参数，并基于计算出的活化能研究胺类型（pKa值）的影响。根据所得结果，使用ASTM E698和Starink方法计算得出的FLM、SER和DOX与乳糖的平均活化能分别为335.23、132.02和270.99 kJ/mol。结果表明，与其他两种抗抑郁药物相比，SER -乳糖混合物中药物与乳糖相互作用的可能性更高，这与其pKa值一致。
