初始非饱和多孔物料对冷冻干燥过程的影响

提出了“初始非饱和多孔物料冷冻干燥”的思想,从实验上验证具有一定初始孔隙的非饱和多孔物料对液体物料冷冻干燥过程的强化作用。设计、加工和组装了一套实验室规模的多功能冷冻干燥装置。采用“液氮制作冰激凌法”,将以甘露醇为主要溶质的液体物料制备成具有不同初始孔隙的冷冻物料。对于相同质量和相同湿含量的非饱和冷冻物料,在相同的操作条件下,进行冷冻干燥实验,并与常规冷冻干燥相比较。结果表明,初始非饱和物料对冷冻干燥过程确实具有显著的强化作用。非饱和冷冻物料(初始饱和度0.28)的干燥时间比常规冷冻物料(初始饱和度1.00)能够节省36.4%。初始饱和度越小,干燥时间越短,干燥产品的含水率越低。     

构建微波冷冻干燥质扩散系数的一种新方法

针对现有微波冷冻干燥模型中必须依靠实验以确定扩散系数的问题．提出一种构建扩散系的新方法。根据毛细管低压气体输运理论，利用物料本身的细微结构、气体分子平均自由程、气体状态参数和气体物性参数来构建扩散系数，在此基础上建立微波冷冻干燥模型。并结合牛肉的微波冷冻干燥行模型可靠性分析。结果表明，新建模型能够很好地描述微波冷冻干燥过程温度场的变化及其特征．升过程干燥曲线的理论值与实验值之间的相对误差小于10％。     

药品冷冻干燥过程的退火机理分析

运用热力学和动力学理论分析了药品冷冻干燥过程中的退火操作改变冻结药品结构的机理。通过对化学势随晶粒曲率半径变化、重结晶过程中冰晶半径随时间变化、非晶态基质的粘度随温度变化几个关系式的分析,得出退火温度必须要高于冻结药品的玻璃化转变温度;最佳退火持续时间与重结晶的速率紧密相关,且是退火温度的函数;退火后再冷却过程的冷却速率不影响升华干燥速率等结论。     

冻干过程在线气体质谱的研究

为了探索检测生化药品真空冷冻干燥过程中冻干室内发生微量漏油和判断升华干燥结束点的有效方法,采用质谱仪对冻干机内硅油泄漏和一次升华干燥过程进行在线监测。结果表明,质谱仪能检测到冻干室内本底硅油量为1×10^-12,当硅油泄漏量为1×10^-6时,采用质谱仪可在15min内检测到;当冻干机空载运行时,采用质谱仪检测N₂、O₂、H₂O、Ar占气体体积分数分别为82.31%、15.68%、1.37%、0.64%,药品在一次升华干燥过程后期,4种气体占气体体积分数分别为82.47%、14.9%、1.75%、0.88%,可用空载冻干室内空气各组分所占比重判断药品一次升华干燥过程的结束。本研究为冻干机内硅油泄漏和生化药品冻干进程的判断提供了新方法。     

On the robustness of the soft sensors used to monitor a vial freeze-drying process

Process monitoring is a key issue in pharmaceutical freeze-drying to evaluate if the limit product temperature is approached, to identify the ending point of the main drying stage, and to estimate the value of some parameters of a mathematical model of the process so that it can be used for cycle optimization. Soft sensors can be used for this purpose: three algorithms, based on the extended Kalman filter and on product temperature measurement, have been compared in this study; they differ on the number of estimated parameters and on the way used to set their initial estimates. Results evidence that the accuracy of estimates is strongly dependent on the initial values of model parameters, and soft sensors #1 and #2 require a preliminary investigation to get accurate initial estimates of the heat and mass transfer coefficients. Soft sensor #2 should be preferred as it just requires an initial estimate of the heat transfer coefficient. Significant advantages are obtained with soft sensor #3: accurate estimates are obtained whichever values of the parameters are used to start the calculations (provided that reasonable values are used) and, thus, it can be effectively used to monitor the freeze-drying cycle without any preliminary investigation. Soft sensor #3 should thus be preferred to the other tools for freeze-drying monitoring.     

Near net shape fabrication of porous cordierite by combination of foam gel-casting and freeze-drying

Near net shape fabrication of porous cordierite was successfully achieved through a combination of foam gel-casting, freeze-drying, and in situ synthesis. Environment friendly gelation was used as gel system, and the gelatin concentration influenced the drying shrinkage vastly. Combined with the volume expansion coming from phase transition and solid reaction during in situ synthesis of cordierite, the total linear shrinkage could be controlled around zero (−1.87% to 0.45%) by adjusting the gelation concentration and solid content in the slurry, meanwhile the prepared porous cordierite ceramics showed both high porosity (85.9%–91.1%) and high compressive strength (0.58–3.37 MPa). The sample with 0.05 g/ml gelatin concentration and 20 vol% solid content possessed excellent performance: total porosity of 89.1%, compressive strength of 1.36 MPa, and specific strength of 4.9 MPa/(g/cm³), showing the potential usage of filter carrier.     

Some implications of structural collapse during freeze-drying using Erwinia caratovoraL-asparaginase as a model

When the enzyme Erwinia caratovora L -asparaginase was freeze-dried in mixtures of lactose and sodium chloride, biological activity and protein structure were preserved during drying. However, by altering the ratios of the excipients in the formulation it was possible to obtain products which were pharmaceutically acceptable or unacceptable as assessed by the criteria of dried cake appearance, moisture content or ease of reconstitution.     

具有预制孔隙多孔介质冷冻干燥的多相传递模型

基于局部质量非平衡假设,建立了多相多孔介质热、质耦合传递数学模型,理论验证具有预制孔隙的初始非饱和多孔物料对冷冻干燥过程的强化作用。模型考虑了多孔介质的吸湿效应,构建了3种吸附-解吸平衡关系。模型使用基于有限元法的COMSOL Multiphysics软件平台数值求解,并与实验数据进行了比较。结果表明,初始非饱和冷冻物料能够有效地强化冷冻干燥过程。采用不同函数形式的吸附-解吸平衡关系模拟的干燥曲线均与实验数据非常吻合。通过分析物料内部的饱和度、温度和质量源分布,探讨了初始非饱和物料冷冻干燥过程的传热传质机理。初始非饱和物料的干燥速率控制因素主要是传热。模拟考察环境辐射温度对冷冻干燥过程影响的结果表明,所建模型具有良好的预测能力。     

冷冻干燥过程相迁移和相分布的孔尺度网络模型与模拟

构建了51×51二维孔-喉网络模型对冷冻干燥过程的升华干燥阶段进行模拟。与传统的连续介质模型相比,孔网络模型的特征是具有跟踪干燥过程中物料内部的干燥前沿和相分布的能力。采用网络模型预测了牛肉和火鸡肉的干燥曲线,并模拟了不同冻结速率的火鸡肉在干燥过程中形成的相分布。讨论了模型的计算特性,并分析了孔径分布对相分布特性的影响。结果表明：网络模型可较好地预测升华干燥阶段,可在孔尺度上揭示干燥过程的动力学机理,将为准确地判断升华干燥与解析干燥的转变点提供理论计算基础。     

减压蜡油加氢裂化反应动力学模型研究进展

阐述了减压瓦斯油（减压蜡油）加氢裂化反应动力学模型的研究进展,包括基于传统集总技术、连续混合物、结构导向集总以及单事件方法的动力学模型,对各模型方法的反应网络以及优缺点作了描述。同时,系统地介绍了基于实验数据、原料组成所计算得到的反应速率常数等相关数据对预测产品组成、产品分布的精确性。     

薄壁复合模压压制工艺对产品界面影响研究

采用两种工艺压制了固体火箭发动机用碳纤维/酚醛-高硅氧玻纤/酚醛分层复合模压(简称复合模压)绝热层。方案一为分别压制预成型的高硅氧玻纤/酚醛毛坯和预成型的碳纤维/酚醛毛坯,分别机加后再将高硅氧玻纤/酚醛毛坯和碳纤维/酚醛毛坯配合后压制至固化态;方案二为先压制一个预成型态的高硅氧玻纤/酚醛毛坯,机加后将高硅氧玻纤/酚醛毛坯放入模具中,再加入碳纤维预混料进行压制至固化态。对两种工艺方案制备的绝热层产品进行了微观形貌和耐烧能力检测。结果表明,方案一所压制的产品高硅氧玻纤/酚醛和碳纤维/酚醛界面出现了裂痕,方案二所压制的产品高硅氧玻纤/酚醛和碳纤维/酚醛界面结合完好,呈现出齿状结合;700℃烧蚀后,方案一的高硅氧玻纤层和碳纤维层分离,方案二的高硅氧玻纤层和碳纤维层则仍然连接在一起,在烧后界面没有发生明显变化,结合完好。     

Influence of the processing variables on the microstructure and properties of gelatin-based scaffolds by freeze-drying

In the last few years, the field of tissue engineering has suffered an exponential growth, and although it is true that the processing parameters affect the properties of the scaffolds, only a few studies have investigated that statement. For that reason, the influence of different parameters involved in the freeze-drying process (container, freezing temperature, pH, and solvent used) on the mechanical and structural properties of gelatin-based scaffolds was analyzed in this study. Thus, rheological measurements and porosity analyses were performed to evaluate the scaffolds obtained. Results indicate that the parameters evaluated modify the mechanical properties of the scaffold, highlighting the option of a plastic mold to contain an acidic protein solution produced using a weak acid (acetic acid) at low concentration (0.05 M) as solvent. On the contrary, only the pH and the freezing temperature led to significant differences in the porosity of these scaffolds, obtaining values higher than 95% for all the systems studied. These results are useful to demonstrate that the control of the different parameters implied in the processing technique allows designing a scaffold with specific properties suitable for different applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47671.     

Fabrication of novel BPO4 ceramic foams using the combination of the direct foaming method and freeze-drying techniques

In this study, ammonium phosphate monobasic and boric acid were used as the primary starting materials to produce BPO₄ powder by solid-state reaction. Using BPO₄ powders as the main raw material, BPO₄ ceramic foams were prepared for the first time using the direct foaming method and freeze-drying techniques. The effects of the additive content and solid loading on the slurry's rheological behavior were investigated, and the microstructures and properties of the as-prepared BPO₄ ceramic foams were examined. The results reveal that the porosity of the BPO₄ ceramic foams synthesized at 1223 K ranged from 84.2% to 90.4%, the compressive strength ranged from .12 MPa to .72 MPa, and the thermal conductivity ranged from .32 W/(m·K) to .74 W/(m·K) (298 K). The findings of this study have great significance for the development of new thermal insulation ceramic materials.     

化工生产中的“界面”现象对工艺设备的影响

分析了化工生产过程设备、管道中存在的各种“界面”现象及其影响，并提出相应对策。     

Data-driven tools for the optimization of a pharmaceutical process through its knowledge-driven model

The use of computationally demanding knowledge-driven models to optimize a process might encounter substantial numerical challenges. Because a model is an abstraction and approximation of the process, calculating the exact model optimum might not be necessary because its industrial implementation is bound to be an approximate one. Here we are exploring an alternative optimization route through a surrogate model. Because one of the decision variables affecting the optimization is time-varying, the Design of Dynamic Experiments is used to estimate the surrogate model. The process considered here is a freeze-drying process widely used in the pharmaceutical industry. The model used is a stochastic model describing the process in great detail. It is shown that the proposed data-driven route calculates the optimum in about 8 h, as opposed to 22 h for the knowledge-driven model, while sacrificing only <15% in the computed value of the process performance.     

Optimization of the freeze-drying process for microemulsion systems

Abstract

The aim of this work was to develop a freeze-dried microemulsion using Design of Experiment and loaded with Amphotericin B, which is quite unstable in aqueous media, as a drug model. Different types of cryoprotectants were studied. The microemulsion containing maltose at 5% (w/w), frozen at a temperature of –80?°C and performed with a 24?h of freeze-drying time, yielded the best results. The freeze-drying process reduced the microemulsion droplet size and does not change the AmB content. Therefore, microemulsions containing maltose are suitable for drug incorporation, and the freeze-drying was able to enhance the drug stability in the system.     

丹参酚酸B水提取动力学研究进展

论述了丹参中丹参酚酸B水提取过程的动力学因素,着重分析了提取温度、提取时间、药材粒度等因素对丹参酚酸提取过程的影响,并借助现有模型来进行描述.     

Influence of inner vapor transfer property of a freeze dryer on the design space of drying process

A freeze dryer with a radiative heating device was constructed and the inner vapor transfer property was regulated by separating the drying chamber and the condenser with an orifice. A mathematical model was used to obtain the contour diagrams of the selected parameters (e.g., product temperature and total drying period) during drying as a function of the heating condition and chamber pressure. Furthermore, the inner vapor transfer coefficients of the freeze dryer were used to draw the operation lines on the diagrams. The combinations of contour diagrams and operation lines clearly depict the design spaces. It was confirmed that the inner vapor transfer property substantially affected the acceptable operation range, and it was revealed that this coefficient is key to quantify the performance of a freeze dryer. This coefficient could also be used to predict the occurrence of choked flow during a freeze-drying run.     

Shear creep analysis of solid rocket motor bonding interface and rapid prediction model**

During vertical storage of solid rocket motors, shear creep behavior occurred at the sidewall bonding interface due to self-weight load, threatening the structural safety and storage life of the motor. To study the shear creep characteristics of the bonding interface, shear creep tests were conducted on a shear interface test piece of a motor under various temperatures and stresses. An engineering criterion for the onset of nonlinear viscoelastic stage of the bonding interface was proposed, and a rapid prediction model for shear creep of motor bonding interface in linear viscoelastic stage was devised. Furthermore, the stress-time master curve of shear creep compliance at the bonding interface was established, revealing the variation trend of shear creep compliance during long-term creep process. The results showed that this rapid prediction model had simple construction, high accuracy and wide applicability, and could well predict short-term creep behaviour of bonding interface in linear viscoelastic stage. A method for structural integrity assessment of vertically stored solid rocket motors could be provided by using these research methods and results.     

超高真空扩散泵油极限真空测试条件的探讨

探讨了274、275超高真空扩散泵油极限真空测试过程中，除气、循环冷却水温度、冷阱及环境温度等因素对测试结果的影响。结果表明，冷阱对测试结果影响不大，除气、循环冷却水温度及环境温度对测试结果影响极大，必须彻底除气同时将温度控制在10～25℃，才能准确测试出极限真空度。