Stability of the Mokohydrate Crystal form of Cefazolin Sodium as a Function of Moisture

Abstract

Moisture effects on the stability of the monohydrate crystal form of cefazolin sodium were investigated. Results show that increased moisture content of this compound adversely affects the microbiological and polarographic stability at elevated temperatures. In addition, butyl rubber stoppers provided more protection against moisture than natural rubber stoppers at higher humidity conditions.     

Effect of moisture content on curing kinetics of agglomerate cork

The curing process of Toluene 2,4-DiIsocyanate (TDI) pre-polymer with granulate cork is significantly affected by the cork moisture content since the reaction of isocyanate is highly sensitive to water. Two types of moisture are considered: the moisture contained inside the granulate cork, residual moisture, and the moisture intentionally sprayed over the granules of cork, added moisture. This study analyses the curing kinetics of TDI and granulate cork mixtures containing added moisture using Differential Scanning Calorimetry (DSC), and the reaction rate increase associated with the added moisture content (AMC). The underlying objective of this work is to reduce the time needed to obtain agglomerate cork stoppers through AMC increase.     

Urokinase: Stability Studies in Solution and Lyophilized Formulations

Urokinase - a serine protease - is used clinically as a thrombolytic agent to dissolve blood clots. Low molecular weight Urokinase (33,000 dalton) isolated from human kidney cells using tissue culture techniques was used in the stability studies. Quantitative determination of Urokinase was accomplished by either amidolytic or fibrinolytic activity assay methods. The degradation of Urokinase in solution at 55 °C follows pseudo-first order kinetics at several pH values. The pH range for maximum stability has been determined to be about 6 to 7.

The stability of Urokinase is very sensitive to the quantity of residual moisture in the lyophilized formulation. Rubber stoppers used as closures for the glass vials were identified as a major source of moisture. The loss of activity from freeze dried formulations was inversely related to the specific activity of tissue culture derived Urokinase. Similar relationship was also observed for the adsorption of Urokinase from 5% dextrose diluent to the surface of polyvinyl chloride large volume parenteral diluent bags. Initial degradation rates (zero order) for freeze dried urokinase formulations with and without the addition of human serum albumin (HSA) as a stabilizer determined at 50, 40 and 30 °C demonstrated that loss of urokinase followed the Arrhenius relationship with an apparent energy of activation (Ea) of 15 kcal per mol. The addition of HSA resulted in an increase in stability by about a factor of four. However, the apparent Ea for the formulations with and without HSA was not significantly different as evident from parallel slopes in the Arrhenius plots.     

Urokinase: Stability Studies in Solution and Lyophilized Formulations

Abstract

Urokinase - a serine protease - is used clinically as a thrombolytic agent to dissolve blood clots. Low molecular weight Urokinase (33,000 dalton) isolated from human kidney cells using tissue culture techniques was used in the stability studies. Quantitative determination of Urokinase was accomplished by either amidolytic or fibrinolytic activity assay methods. The degradation of Urokinase in solution at 55 °C follows pseudo-first order kinetics at several pH values. The pH range for maximum stability has been determined to be about 6 to 7.

The stability of Urokinase is very sensitive to the quantity of residual moisture in the lyophilized formulation. Rubber stoppers used as closures for the glass vials were identified as a major source of moisture. The loss of activity from freeze dried formulations was inversely related to the specific activity of tissue culture derived Urokinase. Similar relationship was also observed for the adsorption of Urokinase from 5% dextrose diluent to the surface of polyvinyl chloride large volume parenteral diluent bags. Initial degradation rates (zero order) for freeze dried urokinase formulations with and without the addition of human serum albumin (HSA) as a stabilizer determined at 50, 40 and 30 °C demonstrated that loss of urokinase followed the Arrhenius relationship with an apparent energy of activation (Ea) of 15 kcal per mol. The addition of HSA resulted in an increase in stability by about a factor of four. However, the apparent Ea for the formulations with and without HSA was not significantly different as evident from parallel slopes in the Arrhenius plots.     

橡胶木吸湿/防霉防腐功能改良研究

目的 为了改善橡胶木吸湿导致的霉变、虫蛀和腐朽等问题，利用改性剂降低橡胶木的吸湿性能，显著改善防霉防腐性能。方法 分别用糠醇、马来酸酐和乙酸酐浸渍处理橡胶木，运用吸湿增重率、动态接触角分析、傅里叶红外光谱(FTIR)分析等方法研究橡胶木的吸湿性能变化;采用空气杂菌、白腐菌和褐腐菌考察其抗生物劣性。结果 药剂处理能不同程度地降低橡胶木的吸湿性能，糠醇和马来酸酐处理材的吸湿率可降低13.13%~67.18%，乙酸酐处理材的吸湿率先增加后下降。生物抗性结果显示，糠醇能显著提升橡胶木的防霉抑菌性，4 h处理材对白腐菌的抗性比素材的提升了45.92%，对褐腐菌的抗性提升了16.61%;马来酸酐和乙酸酐对微生物的生长也有一定抑制效果。结论 采用马来酸酐、糠醇和乙酸酐浸渍橡胶木降低了游离羟基含量，从而降低了橡胶木吸湿性能，显著改善了防霉防腐性，且糠醇浸渍处理4 h的橡胶木可获得最佳的生物抗性。     

Moisture absorption characteristics of rubber particulate filled epoxy adhesives

Results are reported for the moisture absorption characteristics of bisphenol epoxy adhesives containing between 8 and 12% rubber particles by weight. The maximum moisture content and the initial rate of absorption were determined for specimens maintained at temperatures of 23 and 60° C in atmospheres with relative humidities of 12, 76 and 100%. The swelling of samples immersed in water was also determined. Unlike many other epoxy systems, the maximum moisture content was found to vary appreciably with temperature, as well as with relative humidity, and the initial rate of absorption was found to decrease substantially with increasing relative humidity, especially at higher temperatures. While the maximum moisture content was essentially independent of rubber content and cure treatment, the initial rate of absorption was found to be sensitive to both factors.     

A new methodology to evaluate the mechanical properties of elastomeric closures

A quantitative method was developed to evaluate the mechanical properties of elastomeric closures commonly used in liquid parenteral dosage forms. The new methodology was based on the compression of individual stoppers facing upwards, with a stainless steel probe attached to an Instron testing machine. The Instron recorded the maximum force exerted by the closure at a preset rate and displacement value. The mechanical properties were also evaluated with the standard needle penetration force test. The compression test was found to be more sensitive in ascertaining differences in the mechanical properties of stoppers compared to the needle penetration test. Changes in the mechanical properties of closures exposed to various concentrations of acetate buffer, pH and buffer species were also evaluated in this study. The mechanical properties of all stoppers tested were affected by the acetate buffer concentration, even though their physical appearance did not change. The compression force was significantly decreased with an increase in buffer concentration, whereas the needle penetration force values were not significantly different. Since there was no significant effect of pH or citrate buffer species on the mechanical properties of closures, the changes in compression force observed were attributed to the acetate buffer species. In addition, an increase in the duration of the autoclaving cycle significantly affected the mechanical properties of polyisoprene stoppers, whereas the properties of bromo and chlorobutyl stoppers remained unchanged.     

The impact of esterification on the properties of starch/natural rubber composite

The starch was modified by esterification, and the starch/natural rubber composite was prepared by blending the modified starch with natural rubber latex. The morphology, thermal stability and mechanical properties of the composite were investigated. The results show that the crystal structure of starch in the composite disappears after modification with esterification, and the starch particles with an average size around 200 nm homogenously disperse throughout the natural rubber (NR) matrix. The thermal stability of composite is improved significantly after the modification with starch. The mechanical properties of composite are enhanced with the increase of starch loading. The composite possesses the best properties at the starch xanthate content of 20 parts per hundred rubber (phr). The enhanced thermal stability and mechanical properties of modified starch/NR composite are mainly due to the improved phase interface interactions between rubber and starch.     

低苯基硅橡胶的耐热性能研究

讨论了多种氧化铁类合金氧化物对提高低苯基硅橡胶耐热性能的作用。实验结果表明,铁锡氧化物的复合物对提高低苯基硅橡胶耐热性的效果最好,热失重分析说明添加铁锡氧化物的复合物试样的外延起始热分解温度比空白样提高了７０℃。     

How does hydration affect the mechanical properties of wine stoppers?

Data related to the comparison of the mechanical properties of the different stoppers used in the wine industry are scarce. This study aims at comparing the effect of hydration (from 0 to 100 % relative humidity at 25 °C) on the mechanical properties of four widely used types of stoppers: natural corks, agglomerated corks, technical stoppers and synthetic (co-extruded) stoppers. For both natural and agglomerated corks, the Young’s modulus was significantly and similarly affected by hydration, with a constant plateau value up to 50 % relative humidity (RH) and a mean value around 22 and 14 MPa, respectively. For higher RH, the increase in water content leads to a decrease in the material rigidity (Young’s modulus <10 MPa), which is attributed to water clusters formation between polymer chains. Technical stoppers revealed a similar profile, but with a much smaller impact of the water content and with overall lower Young’s moduli values, around 5 MPa, throughout the RH range. The stiffness of synthetic closures was not affected by hydration, in agreement with the hydrophobic behavior of polyethylene. Differential scanning calorimetry and dynamic mechanical thermal analysis allowed us to identify a glass transition temperature (T _g) in cork (around 0 °C), and another one in agglomerated cork and technical stoppers (close to ?45 °C, corresponding to additives). All together, for the first time the data highlight the comparative mechanical properties of such materials of the wine industry, and the progressive loss of the “cork-like” behavior of cork composites when other components are mixed with cork.     

Failure of a Sliding Metal Gate Due to Single-Impact Bending Fracture and Poor Installation Practice

This work looks into the failure of a sliding metal gate and the current practice for installing such sliding gates. The root cause of the failure was fracture of an L-shaped stopper that is very commonly used in sliding metal gates. Although fatigue associated with repeated impacts due to gate opening and closing operations are often blamed for failure of L-shaped stoppers, single-impact bending fracture was implicated in the present case. Besides L-shaped stoppers, it is a common practice to install a small metal stopper in the floor track to prevent gate overrunning. The suitability of installing such stoppers in floor track is questioned in the present study.     

三种耐热剂对全氟聚醚橡胶材料耐热性能的影响

研究了碳纳米管(CNTs)、有机蒙脱土(OMMT)、Fe_2O_3对全氟聚醚(PFPE)橡胶力学性能、压缩永久变形、热稳定性及耐热空气老化性能的影响;采用热分解动力学模型分析了未添加耐热剂的PFPE橡胶的热降解机制。结果表明:CNTs、OMMT、Fe_2O_3均能提高PFPE橡胶基体的热稳定性,其中,CNTs/PFPE橡胶复合材料起始热失重温度及失重5%时的温度相比未添加耐热剂的PFPE橡胶分别提高了32.1℃和29.0℃;Fe_2O_3能明显稳定PFPE橡胶基体在200℃热空气条件下老化72h后的性能。在空气及N_2气氛下,随着升温速率的提高,未添加耐热剂的PFPE橡胶的热失重曲线均向高温方向移动。根据Kissinger方程,计算出PFPE橡胶基体在空气气氛下的热解活化能为135.06kJ/mol,在N_2气氛下的热解活化能为262.46kJ/mol。     

The Effect of Environmental Moisture and Temperature on the Physical Stability of Effervescent Tablets in Foil Laminate Packages Containing Minute Imperfections

The effect of environmental moisture on the physical stability of effervescent tablets in foil laminate packages containing microscopic imperfections (openings) was examined. Packaged tablets were stored at different relative humidity (RH) and temperature conditions and evaluated for physical stability at predetermined time intervals. Physical stability was assessed by noting if the tablet components reacted prematurely to yield soft tablets during storage. A penetrating dye solution test was used to determine if the foil packages contained imperfections which might allow transmission of moisture. The results of the investigation indicated that absolute moisture integrity of the foil package is required for product stability.     

硅橡胶耐热性的研究进展

本文综述了硅橡胶的热氧老化机理,归纳了改善硅橡胶耐热性能的主要途径,指出了提高硅橡胶耐热性能的发展方向。     

Moisture the dominant factor in the stability of doxylamine succinate tablets

During a stability trial at 55°C with doxylamine succinate combined with different excipients at different moisture contents, moisture was found to be the dominant factor affecting the stability of doxylamine succinate. Each excipient however also had a specific affect.     

The Effect of Environmental Moisture and Temperature on the Physical Stability of Effervescent Tablets in Foil Laminate Packages Containing Minute Imperfections

Abstract

The effect of environmental moisture on the physical stability of effervescent tablets in foil laminate packages containing microscopic imperfections (openings) was examined. Packaged tablets were stored at different relative humidity (RH) and temperature conditions and evaluated for physical stability at predetermined time intervals. Physical stability was assessed by noting if the tablet components reacted prematurely to yield soft tablets during storage. A penetrating dye solution test was used to determine if the foil packages contained imperfections which might allow transmission of moisture. The results of the investigation indicated that absolute moisture integrity of the foil package is required for product stability.     

快速凝固天然橡胶的结构和性能的研究

采用硬脂酸、异辛醇以及羟丙基甲基纤维素作为辅助剂制备了快速凝固天然橡胶,并对凝固后天然生胶的结构、加工性能、热稳定性和力学性能进行研究。研究表明快速凝固橡胶的蛋白质含量增加。与乙酸凝固相比,快速凝固天然橡胶具有更高的热稳定性、较低的损耗因子。同时,快速凝固天然橡胶的拉伸强度和撕裂强度相对乙酸凝固天然橡胶分别由18.0 MPa与28.9 kN·m~(-1)提高到21.1 MPa和35.5 kN·m~(-1),交联密度由4.39×10~5 mol/cm~3提高到5.09×10~5 mol/cm~3。     

Area Under the Cureve Estimation in Bioequivalence Studies

Abstract

During a stability trial at 55°C with doxylamine succinate combined with different excipients at different moisture contents, moisture was found to be the dominant factor affecting the stability of doxylamine succinate. Each excipient however also had a specific affect.     

纳米石墨片-羧基丁腈橡胶复合材料结构形态与电性能

利用电子束辐照法制备纳米石墨片(GnPs)-羧基丁腈橡胶(XNBR)复合材料,研究辐射剂量对胶乳共混体系稳定性的影响,并对GnPs-XNBR复合材料的交联度、热稳定性、电性能及其形貌予以表征。结果表明:辐照后GnPs-XNBR复合材料的交联度、热稳定性和体积电阻率提高,而共混乳液的稳定性显著降低。辐照强化了乳胶粒子与石墨片之间的界面结合,形成胶乳粒子包覆石墨片的核-壳结构,进而提高石墨片在基体中分散均匀性,并使GnPs-XNBR复合材料的热稳定性和介电常数提高,导电性和介电损耗降低。     

高硬度有机硅橡胶耐热性能与回弹性能的改善

通过添加气相法白炭黑增加硅橡胶硬度,添加金属氧化物(二氧化铈)改善硅橡胶热稳定性。研究了不同粒径、不同用量二氧化铈对硅橡胶耐热性的影响,并分析了填料对硅橡胶回弹性能的影响。