盐酸环丙沙星的热稳定性和热分解反应动力学研究

目的:用热分析法分析盐酸环丙沙星的热分解过程及机制。方法:以Al2O3为参比物,在氮气条件下采用差示扫描量热法、热重法和微分热重法分析样品,根据热重曲线数据计算出其特征热分解反应表观活化能(E)、指前因子(A)、反应级数n和pk值。结果:E=101.18kJ.mol-1、lnA=26.96s-、n=1、pk=7.01,常温下药品贮存期为2年。结论:用热分析法研究盐酸环丙沙星等固体药物的热分解过程方法简便,结果可靠。     

头孢呋辛钠的热稳定性及其热分解动力学研究

目的:研究头孢呋辛钠的热稳定性。方法:采用热重分析法和差式扫描量热法测定头孢呋辛钠在氮气和空气中的热分解曲线,借助经典的非等温速率方程Kissinger和Ozawa-Flynn-Wall方法计算该药物的热分解动力学参数。结果:2种方法计算头孢呋辛钠在空气中的热分解动力学参数分别为:表观活化能139.2、139.3kJ.mol-1,指前因子(ln值)18.64、18.66s-1;在氮气中上述参数分别为106.8、108.5kJ.mol-1,14.64、14.85s-1。2种计算方法结果无显著性差异。结论:头孢呋辛钠具有很高的活化能,热稳定性好,在氮气中更稳定。     

棓丙酯注射液热降解动力学及稳定性研究

目的:研究棓丙酯注射液的热降解动力学,为药物贮存提供理论依据。方法:采用高效液相色谱法测定药物含量,并以恒温加速法研究在25、30、40℃下,棓丙酯注射液6月内含量变化及其降解规律,用趋势外推法预测棓丙酯注射液不同温度下的有效期。结果:棓丙酯注射液的降解规律符合一级动力学方程,在25、30、40℃下,其有效期分别为21.7、11.3、5.4个月。结论:温度是影响棓丙酯注射液稳定性的重要因素之一,常温下丙酯注射液是稳定的。     

酮康唑涂膜剂热稳定性研究

采用反相高效液相色谱法测定酮康唑涂膜剂中的酮康唑含量,用加温加速实验法研究该涂膜剂的热稳定性动力学。结果表明其降解反应为一级动力学过程,预测其半衰期和有效期分别为11.4年和1.7年。     

尼卡地平的热稳定性及其热解非等温动力学研究

目的　研究尼卡地平的热降解及热稳定性 ,建立动力学方程。方法　采用 TG热重分析仪测定药物的热解曲线 ,用 Achar微分法和 Coats- Redfern积分法及 Ozawa法确定热分解机理函数。以加速稳定性试验对照计算结果。结果　求出了尼卡地平的热解动力学参数——活化能 E,指前因子 A。结论　尼卡地平对热敏感 ,适于低温保存 ;在潮湿环境中更易分解 ,其热解为一级反应 ,动力学方程为 :dα/dt=Ae-Ea/RT(1 -α)。     

TGA热降解动力学方法评价头孢唑林钠的固体稳定性

HPLC法分析头孢唑林钠的TGA热降解残留物，发现其中的主要热降解物和头孢唑林钠在固体贮存中产生的主要降解物相同，提示二者的分解途径相似，据此，利用TGA测定热降解动力学的方法，建立了评价头孢唑林钠固体相对稳定性的方法，虽然头孢唑林钠的热降解反应是一复杂的反应过程，但选择1％的降解水平（conversion level）进行评价可得出和常规加速试验相似的结果，利用建立的评价方法，对头孢唑林钠的三种不同结晶型（α型、脱水α型和无定型）产品的相对稳定性进行评价，发现其α型样品的相对稳定性最好，无定型样品的相对稳定性最差。     

磷酸二氢铵热稳定性的研究

用热分析法对磷酸二氢铵热稳定性进行了研究，其结果对该类复肥的生产、贮存、运输和应用有重要的现实意义。     

核黄素注射液光和热降解动力学的研究

目的　研究核黄素注射液光和热降解动力学的规律。方法　采用恒温加热与光照试验方法。结果　核黄素注射液在光和热共同作用下的反应速率方程为 :-dc/dt =(kheat+klight)c,其中 ,kheat=Aheatexp(-Eaheat/RT) ,klight=Alight·exp(-Ealight/RT)·E。结论　Ealight的数值与光源的种类无关。     

喹诺酮类药物的热稳定性及其热分解非等温动力学研究

目的　研究喹诺酮类药物的热稳定性及热降解,建立动力学方程。方法　用TG-DTG热重仪测定药物的热解曲线，用Achar微分法和Coats-Redfern积分法确定热分解函数。结果　根据TG-DTG热解曲线和红外图谱推断出依诺沙星、诺氟沙星、盐酸芦氟沙星和氧氟沙星等4种喹诺酮类药物的热分解过程并求出其热解动力学参数活化能E、反应级数n和指前因子A及动力学补偿参数。结论　热稳定性为盐酸芦氟沙星>依诺沙星>氧氟沙星>诺氟沙星,它们的热分解过程相同;4种药物胶囊的稳定性均大于各自原药;诺氟沙星、依诺沙星、氧氟沙星的热解机理函数相同，动力学方程为dα/dt=Ae^-E/RT(1-α)²，盐酸芦氟沙星为dα/dt=Ae^-E/RT(1-α)³。     

左金丸及类方药性差异的生物热动力学研究

从生物物理和牛物化学的角度,探讨中医经典类方药性差异的客观真实性.利用微量热法,测定了大肠杆菌在左金丸、甘露散、茱萸丸和反左金丸水煮液作用下的生长热谱曲线,获得相应的生物热动力学参数,结合本草文献报道,综合分析左金丸及类方的药性差异.结果发现,左金丸及类方的水煮液对大肠杆菌的生长代谢表现出不同的活性作用.左金丸具有抑菌作用,而反左金丸对细菌的生长有一定的促进作用,即寒凉药方左金丸和甘露散使细菌指数生长期的生长速率常数减小,发热功率降低.温热药方茱萸丸和反左金丸使细菌指数生长期的生长速率常数增大,生长代谢过程中热量释放显著增加.寒热性能介于两方之间的甘露散和茱萸丸对细菌指数生长期的生长速率常数和热量释放的影响不明显.结果证实4方之间存在较稳定的药性差异,微量热法可作为刻画中医经典类方药性差异的一种新方法.     

氟氯西林钠多晶型非等温热分解动力学

目的:分析固体氟氯西林钠不同晶型的热分解过程。方法:采用TG-DTG技术研究氟氯西林钠不同晶型在动态氮气气氛中的热分解情况。综合运用微分Achar和积分Coats-Redfern两种热分析动力学方法来处理非等温热分解动力学数据。结果:获得各晶型的热分解动力学参数和方程。结论:氟氯西林钠各晶型的热分解动力学参数和热稳定性能存在差异。     

布洛芬的热行为和热分解反应动力学

目的研究布洛芬(ibuprofen)的热分解行为,推导出其最可能的热分解反应机制,并求出相关的动力学参数.方法用TG-DTG技术研究布洛芬在空气气氛中的热分解行为,协同使用4种热分析动力学方程推导出其最可能的热分解反应机制,求出相关的动力学参数.结果布洛芬的热氧分解活化能Eα=94.8 kJ·mol-1,lnA =18.46 s-1;其降解过程符合收缩圆柱体的相界反应模型函数,动力学方程为dα/dt=Ae-Eα/RT2(1-α)1/2;动力学补偿效应数学表达式为lnA=0.251 4Eα-6.763 7,相关系数r=0.999 4.结论推导出了布洛芬热氧分解活化能动力学方程和动力学补偿效应数学表达式,其降解过程符合收缩圆柱体的相界反应模型函数.     

Evaluation of degradation kinetics and physicochemical stability of tenofovir

Tenofovir (TFV) has been proven to prevent the transmission of the Human Immunodeficiency Virus (HIV) through the vagina. But, there is little information available about its stability under various storage and stress conditions. Hence, this study aimed to investigate the degradation behavior and physicochemical stability of TFV using liquid chromatography coupled mass spectrometry (LC‐MS) and solid state X‐ray diffraction (XRD) analyses. The LC‐MS analysis was performed on a QTrap mass spectrometer with an enhanced mass spectrum (EMS) scan in positive mode. A reversed phase C₁₈ column was used as the stationary phase. TFV exhibited degradation under acidic and alkaline hydrolytic conditions. The degradation products with m/z 289.2 and 170 amu have been proposed as 6‐Hydroxy adenine derivative of TFV, and (2‐hydroxypropan‐2‐yloxy) methylphosphonic acid, respectively. A pseudo‐first‐order degradation kinetic allowed for estimating the shelf‐life, half‐life, and time required for 90% degradation of 3.84, 25.34, and 84.22 h in acidic conditions, and 58.26, 384.49, and 1277.75 h in alkaline conditions, respectively. No significant degradation was observed at pH 4.5 (normal cervicovaginal pH) and oxidative stress conditions of 3% and 30% v/v hydrogen peroxide solutions. The shelf life of TFV powder at room temperature was 23 months as calculated by using an Arrhenius plot. The XRD pattern showed that the drug was stable and maintained its original crystallinity under the accelerated and thermal stress conditions applied. Stability analyses revealed that the TFV was stable in various stress conditions; however, formulation strategies should be implemented to protect it in strong acidic and alkaline environments. Copyright © 2014 John Wiley & Sons, Ltd.     

甲磺酸非诺多泮的化学降解动力学及其制剂的有效期预测

目的：研究甲磺酸非诺多泮的化学降解动力学,来预测制剂的有效期。方法：采用经典恒温法对甲磺酸非诺多泮溶液和甲磺酸非诺多泮注射剂在不同温度不同时间的含量和有关物质进行考察,采用反相高效液相色谱法进行定量分析,通过数学拟合,确定反应动力学方程,求出反应速率常数K。并运用Arrhenius公式,预测甲磺酸非诺多泮溶液和注射剂在常温下的有效期。结果：甲磺酸非诺多泮溶液和注射剂的含量下降符合一级动力学模型,有关物质增加符合零级动力学模型。甲磺酸非诺多泮溶液在25℃时的t0．9为1．09年,其注射剂在25℃时的t0．9为5．12年。结论：通过制剂学手段,显著提高了甲磺酸非诺多泮注射剂的稳定性。     

基因毒性杂质甲磺酸酯稳定性及水解反应动力学研究

目的:在痕量水平基因毒性杂质甲磺酸酯(甲磺酸甲酯、甲磺酸乙酯、甲磺酸丙酯和甲磺酸异丙酯)的稳定性及水解动力学研究.方法:以乙腈-水(80∶20,v/v)为溶剂配制甲磺酸酯混合溶液,分别置于298、313及323 K温度下,定时取样并加入碘化钠衍生化溶液,分别得到相应的碘代烷烃(碘甲烷、碘乙烷、碘丙烷和碘代异丙烷),采用...     

Thermal and alkaline stability of meropenem: degradation products and cytotoxicity

The stability of the broad-spectrum antibiotic meropenem was investigated in order to isolate and elucidate the mean degradation products involved in thermal and alkaline decomposition of meropenem in solution. The purification of thermal degradation product (45 °C) involved a combination of preparative chromatographic techniques. The degradates were characterized by NMR and ESI-MS. The thermal degradation product was a result of several chemical reactions, with modification of side chain and β-lactam ring, resulting in a pyrrolic derivative. Under alkaline conditions (NaOH 0.1 N), meropenem was converted totally to the corresponding β-lactam ring-opened derivative, in sodium salt state. The degraded samples of meropenem reconstituted solution, powder for injection and alkaline solution was also studied in order to determine the preliminary cytotoxicity in vitro against mononuclear cells. The results obtained indicated that samples could be toxic in high concentration (2.0 mg/mL) after 48 h of incubation. The present study confirms the lability of the drug in aqueous solution, specially when submitted to thermal and alkaline conditions. Thus, it is necessary attention during the handling and storage of this antibiotic.     

碘昔兰注射液的光分解反应动力学初步研究*

目的:研究碘昔兰注射液在4500 lx光照下的光分解反应动力学。方法:测定碘昔兰注射液在4500lx光照下分解产生碘离子及溶液pH值随时间的变化,计算出碘昔兰注射液4500 lx光照下的光分解反应速率常数。结果:碘昔兰注射液4500 lx光照下的光分解反应为一级反应,光分解反应速率常数为3.97×10-5.d-1。结论:碘昔兰注射液在强光下有一定分解,应避光保存。     

荧光光谱法研究清开灵注射液热稳定性

目的对清开灵注射液热稳定性进行初步探讨.方法采用荧光光谱法考察清开灵注射液在不同温度条件、不同存放时间的荧光谱图变化.结果恒温(40、80 ℃)条件下、不同存放时间的热稳定性的荧光谱图,呈现出规律性的变化,通过其谱图的分析,能够反映出不同温度下时间分辨光谱的差异、谱峰强度的差异及不同厂家成品间热稳定性的差异.结论荧光光谱法能够准确地对中药注射剂的热稳定性进行判定,为中药注射剂稳定性的研究和控制提供一种新的途径.     

Photo- and thermal degradation of piroxicam in aqueous solution

Light and temperature have considerable effect on the degradation of piroxicam in aqueous solutions. The pH and acetate buffer ions also affect the degradation process. The apparent first-order rate constants for the photochemical and thermal degradation of piroxicam have been determined as 2.04-10.01 and 0.86-3.06×10(-3) min(-1), respectively. The first-order plots for the degradation of piroxicam showed good linearity within a range of 20-50% loss of piroxicam at pH 2.0-12.0. The rate-pH profile for the photodegradation of piroxicam is a U-shaped curve and for the thermal degradation a bell-shaped curve in the pH range of 2.0-12.0. The thermal degradation of piroxicam was maximum around pH 6.0. It is increased in the presence of acetate ions but was not affected by citrate and phosphate ions.     

Thermal Stability and Degradation Kinetics of Patulin in Highly Acidic Conditions: Impact of Cysteine

The thermal stability and degradation kinetics of patulin (PAT, 10 μmol/L) in pH 3.5 of phosphoric-citric acid buffer solutions in the absence and presence of cysteine (CYS, 30 μmol/L) were investigated at temperatures ranging from 90 to 150 °C. The zero-, first-, and second-order models and the Weibull model were used to fit the degradation process of patulin. Both the first-order kinetic model and Weibull model better described the degradation of patulin in the presence of cysteine while it was complexed to simulate them in the absence of cysteine with various models at different temperatures based on the correlation coefficients (R² > 0.90). At the same reaction time, cysteine and temperature significantly affected the degradation efficiency of patulin in highly acidic conditions (p < 0.01). The rate constants (k_T) for patulin degradation with cysteine (0.0036–0.3200 μg/L·min) were far more than those of treatments without cysteine (0.0012–0.1614 μg/L·min), and the activation energy (E_a = 43.89 kJ/mol) was far less than that of treatment without cysteine (61.74 kJ/mol). Increasing temperature could obviously improve the degradation efficiency of patulin, regardless of the presence of cysteine. Thus, both cysteine and high temperature decreased the stability of patulin in highly acidic conditions and improved its degradation efficiency, which could be applied to guide the detoxification of patulin by cysteine in the juice processing industry.