穿琥宁注射液中DAS-K的含量测定和贮存期的预测

用恒温加速试验法对２％穿琥宁注射液贮存期进行预测并用紫外分光光度法在２５０ｎｍ处测定脱水穿心莲内酯琥珀酸半酯单钾盐吸光度,预测出室温下穿琥宁注射液贮存期为２．３１年。     

穿琥宁注射液与5种输液配伍的稳定性

目的考察室温下穿琥宁注射液与5种常用输液配伍的稳定性。方法采用紫外分光光度法测定配伍后0～8h内穿琥宁的含量变化,同时观察配伍液的pH值、外观及穿琥宁紫外吸收光谱的变化。结果室温下8h内,穿琥宁注射液与5种输液配伍后pH值、外观、含量及紫外吸收光谱均无显著变化。结论穿琥宁注射液可与5种输液配伍应用。     

穿琥宁注射液与5种输液配伍的稳定性考察

目的：考察室温下穿琥宁注射液与5种输液配伍的稳定性。方法：采用紫外分光光度法测定配伍后0～8h内穿琥宁含量的变化，同时现察配伍液的pH值、外观及穿琥宁紫外吸收光谱的变化。结果：室温下8h内，穿琥宁注射液与5种输液配伍后pH值、外观及紫外吸收光谱均无显变化。结论：穿琥宁注射液可与5种输液配伍应用。     

穿琥宁氯化钠注射液的工艺研究

目的：为提高穿琥宁氯化钠注射液的质量，优选穿琥宁氯化钠注射液的最佳处方和制备工艺。方法：采用氯化钠调节等渗、磷酸盐缓冲液对调节pH值、活性炭吸附热原、筛选合适的抗氧剂等手段优化穿琥宁氯化钠注射液的制备工艺，采用高效液相色谱法测定穿琥宁氯化钠注射液的含量。结果：每100m1注射液中含0．193gNa2HP0a和0．131gNaH2PO4时注射液最稳定；抗氧剂为0．1％L-半胱氨酸盐酸盐；45℃为主药的溶解温度；浓配液先加热煮沸15min，再稀配、灭菌，注射液澄明度达到要求；整个制备过程通高纯度N2以隔离空气中的O2。结论：优选的处方和制备工艺，可提高穿琥宁氯化钠注射液的质量。     

盐酸格拉司琼注射液的处方筛选及稳定性研究

目的制备盐酸格拉司琼注射液并考察其稳定性。方法以外观色泽、澄明度、有关物质、含量、pH为指标,筛选处方,考察3批样品的稳定性。结果最佳处方关键因素为pH5.0~7.0,加入辅料聚乙烯吡咯烷酮(PVP)0.2%;以该处方制备的3批样品在市售包装条件下经加速、室温留样考察,质量稳定。结论该处方设计合理,注射液质量稳定。     

穿琥宁注射液与24种药物配伍的稳定性考察

目的：研究穿琥宁注射液与临床常用２４种药物配伍的稳定性,方法：考察穿琥宁注射液与２４种药物在室温下配伍后外观,ｐＨ微粒和紫外吸收度,结果：穿琥宁注射液与庆大霉素,丁氨卡那霉素,环丙沙星,氧氟沙星配伍产生沉淀,与ＶｉｔＣ,ＶｉｔＢ６,ＡＴＰ辅酶Ａ,胞二磷胆碱,氨茶碱,氢化考的松,地塞米松,三氮唑核苷,阿昔洛韦,双黄连,青霉素钠,氨苄西林钠,红霉素,头孢唑啉钠,头孢哌酮钠,头孢曲松钠,头孢呋辛钠,甲硝     

穿琥宁注射液在6种输液中的稳定性考察

研究穿琥宁注射液在６种常用输液中的稳定性。方法：应用紫外分光光度计、酸度计、注射液微粒分析仪分别考察穿琥宁注射液与６种输液配伍后在不同温度下的外观、含量、ｐＨ、微粒及紫外吸收光谱的变化。结果：穿琥宁注射液与６种输液配伍后外观、ｐＨ、微粒、含量、紫外吸收光谱均无显著变化。结论：穿琥宁注射液可与６种输液配伍应用。     

穿琥宁注射液的体外细胞毒性考察

目的 用体外细胞毒性试验考察穿琥宁注射液的安全性,并考察辅料和有关物质对注射液安全性的影响.方法 选用L-929细胞,采用MTT比色法测定不同厂家穿琥宁注射液的体外细胞毒性.结果 不同厂家穿琥宁注射液的安全浓度有差异;辅料的安全浓度高且不同厂家间有差异;有关物质合格的注射液的安全浓度高于不合格的注射液.结论 辅料对穿琥宁注射液的安全性影响较小;有关物质可能影响穿琥宁注射液的安全性.     

甲硝唑G注射液化学稳定性的研究

本文采用化学动力学方法,对甲硝唑葡萄糖注射液的稳定性进行考察,并预测其室温条件下的贮存期.实验结果表明:甲硝唑葡萄糖注射液在pH3.7～5.5之间对热是稳定的。有效期为2年(t_(0.9)~(20℃)=2年)     

星点设计效应面法优选穿琥宁固体脂质微粒处方

目的:应用星点设计效应面法优选穿琥宁固体脂质微粒的处方。方法:以乳化-溶剂挥发法制备穿琥宁固体脂质微粒,以包封率、平均粒径为评价指标,考察内水相与油相体积比(W1/O)、脂质比(SA/SPC,m/m)、外水相表面活性剂(即泊洛沙姆)质量分数对处方的影响,对结果分别进行多元线性与二项式方程拟合,采用效应面预测最佳处方。结果:最佳处方为W1/O为0.2∶0.2,SA/SPC为8∶1(m/m),泊洛沙姆质量分数为1.0%。二项式拟合方程优于多元线性回归方程,但相关性较差。此条件下,包封率为54.90%、平均粒径为(6.27±0.08)μm。结论:所选处方制备的穿琥宁固体脂质微粒质量合格、重现性好,可为该制剂的进一步研发提供参考。     

1′-乙酰氧基胡椒酚乙酸酯注射液的稳定性研究及有效期预测

目的:考察1′-乙酰氧基胡椒酚乙酸酯(ACA)注射液的稳定性,预测其有效期。方法:采用高效液相色谱法测定注射液中ACA含量,考察ACA注射液在高温40℃、光照(4500±500)lx条件下的稳定性,并以经典恒温法得到其分解速率常数K,预测有效期。结果:ACA检测浓度线性范围为5～100μg·mL-(1(r=0.9999,n=5),平均回收率为99.76%,RSD=0.43%。在高温和光照条件下,ACA注射液含量下降,有关物质有所增加。25℃药物分解速率常数K及有效期分别为1.0156×10-5h-1、1.2年。结论:本品对光、热较敏感,高温不利于ACA注射液的稳定,需置于避光阴凉处保存。     

初匀速法预测复方枸橼酸钠注射液的有效期

目的:以初匀速法预测复方枸橼酸钠注射液有效期。方法:采用7个温度对样品进行加速试验,考察葡萄糖降解反应初均速(V0)与开尔文温度的倒数(1/T)的关系,并计算反应活化能、药物反应速度常数及有效期。结果:回归方程为lgV0=18.15—6774.6×1/T(r=—0.9375),复方枸橼酸钠注射液的反应活化能为31.0Kcal·mol-1,20℃药物反应速度常数为1.1×10-5h-1,有效期为1.09y。结论:本方法操作简便,可准确预测复方枸橼酸钠注射液的有效期。     

Rapid and accurate prediction of degradant formation rates in pharmaceutical formulations using high-performance liquid chromatography-mass spectrometry

Rapid and accurate stability prediction is essential to pharmaceutical formulation development. Commonly used stability prediction methods include monitoring parent drug loss at intended storage conditions or initial rate determination of degradants under accelerated conditions. Monitoring parent drug loss at the intended storage condition does not provide a rapid and accurate stability assessment because often <0.5% drug loss is all that can be observed in a realistic time frame, while the accelerated initial rate method in conjunction with extrapolation of rate constants using the Arrhenius or Eyring equations often introduces large errors in shelf-life prediction. In this study, the shelf life prediction of a model pharmaceutical preparation utilizing sensitive high-performance liquid chromatography-mass spectrometry (LC/MS) to directly quantitate degradant formation rates at the intended storage condition is proposed. This method was compared to traditional shelf life prediction approaches in terms of time required to predict shelf life and associated error in shelf life estimation. Results demonstrated that the proposed LC/MS method using initial rates analysis provided significantly improved confidence intervals for the predicted shelf life and required less overall time and effort to obtain the stability estimation compared to the other methods evaluated.     

Solubility and stability of indomethacin in arginine-assisted solubilization system

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID).It is practically insoluble in water, which precludes its use in aqueous solution formulations. The effect of arginine on the solubility of indomethacin was investigated in this study. The solubility enhancement of indomethacin by the arginine was observed. Aqueous solution formulation and freeze-drying formulation using arginine as hydrotropes were developed and studied for physical and chemical stability. Freeze-drying is considered as a suitable formulation to enhance shelf life of indomethacin.     

布洛芬精氨酸盐注射液的制备及稳定性考察

目的:制备布洛芬精氨酸盐注射液并对其进行稳定性考察。方法:优化处方工艺后对布洛芬精氨酸盐注射液进行稳定性考察。采用反相高效液相色谱法测定布洛芬含量。结果:影响因素试验、加速试验及长期试验结果表明,布洛芬精氨酸盐注射液稳定。结论:布洛芬精氨酸盐注射液处方设计合理,工艺可行,质量稳定。     

Statistical evaluation for stability studies under stress storage conditions.

During the pharmaceutical development of a new drug, it is necessary to select as soon as possible the formulation with the best stability characteristics. The current International Commission for Harmonisation (ICH) regulations regarding stability testing requirements for a Registration Application provide the stress testing conditions with the aim of assessing the effect of severe conditions on the drug product. In practice, the well-known Arrhenius theory is still used to make a rapid stability prediction, to estimate a drug product shelf life during early stages of its pharmaceutical development. In this work, both the planning of a stress stability study to obtain a correct stability prediction from a temperature extrapolation and the suitable data treatment to discern the reliability of the stability results are discussed. The study was focused on the early formulation step of a very stable drug, Mitonafide (antineoplastic agent), formulated in a parenteral solution and in tablets. It was observed, for the solid system, that the extrapolated results using Arrhenius theory might be statistically good, but far from the real situation if the stability study is not designed in a correct way. The statistical data treatment and the stress-stability test proposed in this work are suitable to make a reliable stability prediction of different formulations with the same drug, within its pharmaceutical development.     

Stability and transdermal absorption of topical amphotericin B liposome formulations

The aim of this study was to characterize the stability and transdermal absorption of amphotericin B (AmB: 0.05 mg/mg lipid) in hydrogenated soya phosphatidylcholine/cholesterol/charged lipid {dicetyl phosphate (−) or stearylamine (+)} liposomes at molar ratios of 1:1:0, 7:2:0, 7:2:1(−) and 7:2:1(+). The AmB contents in liposomes were determined by HPLC with UV detection at 382 nm. Stabilities of AmB in liposome formulations were compared with those in solution and powder forms, during storage at 4, 30 and 45 °C for 90 days. Absorption studies of AmB across the rat skin were conducted, using vertical Franz diffusion cells at 37 °C for 24 h. The slowest degradation was observed in the positive liposome (7:2:1(+)AmB), with shelf life of 1 year (30 °C). In comparison, the shelf lives of AmB in solution and powder were 4 and 14 days, respectively. AmB in positive liposomes seemed to demonstrate the highest flux in stratum corneum (58 ng/cm²/h), while the highest flux in viable epidermis (23 ng/cm²/h) was observed in negative liposomes. AmB entrapped in charged liposomes showed sustained skin absorption. The positively charged liposome might be the best formulation for AmB, due to its higher stability than other formulations.     

替硝唑葡萄糖注射液的稳定性研究

采用反相ＨＰＬＣ法测定替硝唑葡萄糖注射液中替硝唑的含量，用加温加速实验研究该制剂的热稳定动力学。结果表明，替硝唑的热降解反应为一级动力学过程，在５０、６５、８０、９５℃时的降解速度常数分别为５．５８×１０－４、２．６６×１０－３、８．１０×１０－３、２．８２×１０－２ｄ－１，为８．３年，半衰期为３９．５年。     

兽用诺氟沙星注射液的稳定性研究

用光照和初均速法对兽用诺氟沙星注射液的光稳定性和热稳定性进行了考察，并用美国ＦＤＡ低温考察法和室温留样观察法考察其贮存期。结果表明，本品稳定性好，有效期达２年以上。     

One- and Two-Stage Arrhenius Models for Pharmaceutical Shelf Life Prediction

One of the most challenging aspects of the pharmaceutical development is the demonstration and estimation of chemical stability. It is imperative that pharmaceutical products be stable for two or more years. Long-term stability studies are required to support such shelf life claim at registration. However, during drug development to facilitate formulation and dosage form selection, an accelerated stability study with stressed storage condition is preferred to quickly obtain a good prediction of shelf life under ambient storage conditions. Such a prediction typically uses Arrhenius equation that describes relationship between degradation rate and temperature (and humidity). Existing methods usually rely on the assumption of normality of the errors. In addition, shelf life projection is usually based on confidence band of a regression line. However, the coverage probability of a method is often overlooked or under-reported. In this paper, we introduce two nonparametric bootstrap procedures for shelf life estimation based on accelerated stability testing, and compare them with a one-stage nonlinear Arrhenius prediction model. Our simulation results demonstrate that one-stage nonlinear Arrhenius method has significant lower coverage than nominal levels. Our bootstrap method gave better coverage and led to a shelf life prediction closer to that based on long-term stability data.