【作者】 赵强；

【导师】 詹先成；

【作者基本信息】 四川大学 ， 药剂学， 2004， 博士

【摘要】 研究环境相对湿度对固体药物稳定性的影响,对提高药物的稳定性,提供合理的贮存条件和预测药物的贮存期等都有重要的理论及实用意义。然而,由于试验方法及技术上的复杂性,目前国内外在湿度对药物稳定性影响方面的研究无论从理论上及应用上均远不如对热降解反应的研究详尽。目前国内外在这类研究中,都采用经典恒温恒湿加速试验。在研究药物对热稳定性时,采用程序升温加速试验来代替恒温加速试验,可大大减少试验次数。这就提示我们,在研究药物对湿度的稳定性时,若能在一次加速试验中按一定的规律连续改变相对湿度,也可能具有同样的优点。从理论上分析,我们可用两次试验来取代目前的数十次试验,一次是在恒湿条件下进行的程序变温加速试验,以获得与温度有关的动力学参数;另一次是在恒温条件下进行的程序变湿加速试验,以获得与湿度有关的动力学参数。 作者使用程序控温控湿箱实现了程序变湿和程序变温。以青霉素钾降解动力学研究为例,通过一次程序变湿和一次程序变温加速试验,得到了与温度和湿度有关的全部动力学参数,验证了这一新的试验方法。 青霉素钾的恒温恒湿试验表明,其降解动力学符合公式-dc/dt=k（c₀-c+0.00048）,这里c为青霉素钾在t时刻的含量,c₀是初始含量,k为速率常数。k与温度和湿度的关系可表示为k=Aexp（mRH）exp（-E_a/（RT））,更多还原

【Abstract】 Studying the effect of relative humidity and temperature on the drug stability is of great theoretical and practical importance in enhancing the drug stability, providing reasonable shelf condition and estimating the drug’s shelf life. However, due to the complexity of testing method and skills, studies at home and abroad, both in theories and practice, on the effect of humidity on the drug stability, are not as much as that on thermo degrading reaction.At present, traditional constant temperature and humidity drug stability experiment is widely adopted in this kind of studies. In the studies on the effect of heating on the drug stability, programmed heating drug stability experiment saves more times than the constant temperature experiment, which reminds us that in the studies on the effect of humidity, this might be feasible in the test by continuously changing the relative humidity according to certain rules. In the theoretical analysis, two experiments can be adopted to take the place of numbers of tests, namelyprogrammed heating experiment to obtain the kinetics parameter related to temperature and programmed humidifying experiment to obtain the kinetics parameter related to humidity.Program controlled humidity and temperature oven has been used to programmed humidity and temperature. In the case of penicillin potassium, all the kinetic parameters were obtained by programmed humidifying and programmed heating experiments.Constant humidity and temperature experiments indicate that thedc degradation kinetic can be expressed as-----= k(cQ -c + 0.00048), where,dt the k can be expressed by humidity and temperature ask = y4exp(jwi?//)exp(----—) ? The relationship between content and time atRTconstant temperature by linear humidifying RH = RH0 -0.08/ is expressed as[ln(c0 - c + 0.00048)- In0.00048] = Aexp(----^){-----—exp(mRH0 )[exp(-0.08mO -1]} ■RT 0.08/wAnalyzing the data from experiments, m and -Aexp(----—) were obtainedRTby linear regress [ln(c0 - c + 0.00048) - In0.00048] to{--------exp(mJy/0)[exp(-0.08jM/)-l]}. The relationship between content and0.08mtime at constant humidity by reciprocal heating--------= -6xlO~7f isTo Texpressed as[ln(c0 -c + 0.00048) - In0.00048] = A exp(mRH){--------^—exp(—^-)[exp(-6xl° ￡°f -1]}.6 x 10 Ea RT0 RAnalyzing the data from experiments, Ea and Aexp(mRH) were obtained by linear regress [m(c0 - c + 0.00048) - In0.00048] to& , Ea u , 6x\0’n E J , . , , , . . .-exo(-----^)FexD(---------------—11! ? A can be calculated bypv _ v\ R iipsimultaneous equations from m andy4exp(-----—) obtained by programmedRThumidifying experiment at constant temperature and Ea and Aexp(mRH) obtained by programmed heating experiment at constant humidity.Simulate experiments obtained by Basic language programs show that programmed humidifying and heating experiments are feasible.更多还原