Developing super-hydrophobic and corrosion-resistant coating on magnesium-lithium alloy via one-step hydrothermal processing

Formation of super-hydrophobic and corrosion-resistant coatings can provide significant corrosion protection to magnesium alloys.However,it remains a grand challenge to produce such coatings for magnesium-lithium alloys due to their high chemical reactivity.Herein,a one-step hydrothermal processing was developed using a stearic-acid-based precursor medium,which enables the hydrothermal conversion and the formation of low surface energy materials concurrently to produce the super-hydrophobic and corrosion-resistant coating.The multiscale microstructures with nanoscale stacks and microscale spheres on the surface,as well as the through-thickness stearates,lead to the super-hydrophobicity and excellent corrosion resistance of the obtained coating.

Preparation of Ephedra houttuynia Granule and Its Therapeutic Mechanism of Anti-Mycoplasma gallisepticum Infection Based on Network Pharmacology

The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra houttuynia granule for the treatment of Mycoplasma galliscepticum(MG)infection was prepared.Furthermore,its action mechanism was explored through network pharmacology.The optimal extraction and granulation processes of the compound were determined by high performance liquid chromatography(HPLC)method and L9 orthogonal test,and in the treatment experiment,Ephedra houttuynia granule showed a significant therapeutic effect on MG infection.In the study of network pharmacology,the results showed that the core targets of Ephedra houttuynia granule against MG infection were vascular endothelial growth factor(VEGFA),fos proto-oncogene(FOS),prepro-coagulation factor II(F2),etc.,the gene ontology/kyoto encyclopedia of genes and genomes(GO/KEGG)analysis results indicated that the signaling pathways of neuroactive ligand receptor interaction,cAMP,IL-17,T cell receptor,and tumor necrosis factor(TNF)might involve in anti-MG infection.In conclusion,this study would provide a new idea for elucidating the action mechanism of other diseases in veterinary clinic,which had a certain guiding significance.

Effects of granulation process variables on the physical properties of dosage forms by combination of experimental design and principal component analysis

The current study was to understand how process variables of high shear wet granulations affect physical properties of granules and tablets. The knowledge gained was intended to be used for Quality-by-Design based process design and optimization. The variables were selected based on the risk assessment as impeller speed, liquid addition rate, and wet massing time. Formulation compositions were kept constant to minimize their influence on granules properties. Multiple linear regression models were built providing understanding of the impact of each variable on granule hardness, Carr’s index, tablet tensile strength, surface mean diameter of granules, and compression behavior. The experimental results showed that the impact of impeller speed was more dominant compared to wet massing time and water addition rate. The results also revealed that quality of granules and tablets could be optimized by adjusting specific process variables(impeller speed 1193 rpm, water spray rate 3.7 ml/min, and wet massing time 2.84 min). Overall desirability was 0.84 suggesting that the response values were closer to the target one. The SEM image of granules showed that spherical and smooth granules produced at higher impeller speed, whereas rough and irregular shape granules at lower speed. Moreover, multivariate data analysis demonstrated that impeller speed and massing time had strong correlation with the granule and tablet properties. In overall, the combined experimental design and principal component analysis approach allowed to better understand the correlation between process variables and granules and tablet attributes.

Granulation process analysis technologies and potential applications in traditional Chinese medicine

Pharmaceutical production is changing from batch production to continuous production,during which granulation is one of the most important unit operations.The quality of mass-produced products is traditionally guaranteed by conducting off-line testing,which cannot meet the demand of continuous production for real-time monitoring of critical process parameters and critical quality attributes(CQAs)of the pharmaceutical granulation technology.Since the U.S.Food and Drug Administration proposed process analytical technology(PAT)in 2004,many PAT tools have been developed to monitor the granulation process and provide information regarding the granulation operation conditions and endpoint determination.In this article,we review the recent research and application of two PAT modes in the granulation process,namely,single CQA and multi-CQA PAT,with the aim to provide references for comprehensively improving the technological level of the pharmaceutical granulation process.Furthermore,the potential applications in traditional Chinese Medicine are discussed.

Fluidised bed granulation of two APIs:QbD approach and development of a NIR in-line monitoring method

The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.

Heat Transfer Analysis During "One-Step" Directional Solidification Process for Giant Magnetostrictive Materials

By theoretical analysis of heat transfer during the "one-step" directional solidification process, the functional relation between the temperature in solid-liquid interface and its effect factor was studied. The thermal gradient in solid liquid interface and heat transfer coefficient between the samples and surroundings were also calculated. On the basis of the above analysis, some suggestions for improving the thermal gradient in solid-liquid interface were put forward. It will provide a theoretical instruction for preparing high performance giant magnetostrictive materials (GMM).

Pyramidal and Granule Cells Distribution through Hippocampal Fields: An Index for Sensory Information Processing

Background: This work aims at investigating the histology of hippocampus formation as structural model of information processing. The study addressed the question whether the pattern of cellular type distribution within hippocampal fields could be used as support of information processing in the hippocampus. Method: Pyramidal-shaped neurons presenting both cytoplasm and nucleus outlined clearly were measured systematically on brain slides, using a light microscope connected to a microcomputer equipped with a scanner software for measuring particles. Morphological types of cells were identified following class sizes and their distribution determined through hippocampal fields. Results: A battery of statistical tests: Sturges’ classification, class sizes distribution around overall mean, Bartlett’s sphericity test, principal components analysis (PCA) followed by correlations matrix analysis and ANOVA allowed two cellular groups to be identified in the hippocampus: large and small pyramidal-shaped cells. Conclusion: The results show that sensory information processing in the hippocampus could be built on two classes of pyramidal neurons that differed anatomically with probably different physiological functions. The study suggests combination ensembles clustering large and small pyramidal cells at different rates, as fundamental signaling units of the hippocampus.

Study on Preparation Process and Quality Standard of Tianlu Tongluo Granules

[Objectives]This study was conducted to optimize the preparation process of Tianlu Tongluo Granules and establish its quality standard.[Methods]Tianlu Tongluo Granules was prepared by an orthogonal test.TLC was used to identify Radix Astragali preparata,Radix Paeoniae Alba,Scutellariae Radix and Acori Tatarinowii Rhizoma in the granules,and the content of paeoniflorin in the finished product was determined by HPLC.[Results]The extraction process of Tianlu Tongluo Granules was as follows:adding 6 times of water,and decocting twice,1 h/time.In the forming process,the optimal ratio of thick paste to excipients as 10∶8.6,and the optimal ratio of excipients dextrin:starch:colloidal silicon dioxide was 6.5∶0.5∶1.6.The results showed that TLC spots were obvious,the separation was significant,and the specificity was strong.The paeoniflorin content had a good linear relationship in the concentration range of 5.9048-590.48 mg/L(r=0.9999).The average sample recovery was 101.10%,and the RSD was 1.18%.[Conclusions]The preparation process is stable and reasonable,and the established quality control method is specific and reproducible,and can be used for the quality control of Tianlu Tongluo Granules.

Study on the Forming Process of Yi Medicine Tongfeng Granules

[Objectives]To optimize the forming process of Yi medicine Tongfeng Granules.[Methods]The forming process of Yi medicine Tongfeng Granules was optimized,with paste density,ethanol volume fraction,and type and proportion of excipient as influencing factors,and granule formability,solubility,moisture absorption,and angle of repose as evaluation indicators.Critical relative humidity(CRH)was investigated to select optimal storage conditions.[Results]Maltodextrin was selected as the excipient,and the best process parameters was the ratio of drug to excipient at 1∶2(g/g),under which the forming rate,solubility,moisture absorption rate,and angle of repose were 81.38%,98.90%,8.81%,and 27.5°,respectively.The critical relative humidity was 72%.[Conclusions]The forming process adopted is reasonable and feasible,and can provide a reference for large-scale production of Yi medicine Tongfeng Granules.

Effects of Post-expanding Lower Temperature Granulating Process on Growth Performance of Piglets

[Objective] The paper was to compare the effects of traditional granulating process and post-expanding lower temperature granulating process on starch gelatinization degree and in vitro protein digestibility of conversation feed, and growth performance of piglets. [Method] Sixty weaned piglets, 25 days old, were randomly divided into two groups, six replicates each group, and each replicate contained five piglets. Piglets in control group were fed with the conversation feed developed by traditional granulating process, and those in experimental group were fed with the conservation feed developed by post-expanding lower temperature granulating process. The trial lasted 28 d. [Result] Compared to traditional granulating process, post-expanding lower temperature granulating process significantly enhanced starch gelatinization degree of conservation feed by56.9%（P〈0.05）, and significantly improved in vitro protein digestibility of conservation feed by 11.48%（P〈0.05）. Compared to the control group, the feed intake of piglets in experimental group was increased by 21.63%（P〈0.05）; the average daily gain was increased by 27.61%（P〈0.05）; the diarrhea rate was lowered; and the feed gain ratio was improved by 4.51%（P〉0.05）. The results suggested that post-expanding lower temperature granulating process effectively enhanced feed digestion and absorption of piglets. [Conclusion] The paper provides a theoretical basis and practical reference for improvement of production process of conservation feed.

预造球强化难制粒精矿烧结工艺

随着进口铁矿石价格的增长,充分利用廉价的难处理铁矿资源成为钢铁企业降本增效的关键。本文针对难制粒精矿在烧结中利用率低的问题,在复合造块法的基础上开发了预造球工艺,显著提高了难制粒精矿的配入量,有效改善了制粒效果与烧结产、质量指标。研究表明,在难制粒精矿配比达到36%时,采用预造球制粒可以使准颗粒平均粒径提高1.53 mm,透气性指数提高0.17。在此基础上,垂直烧结速度提高13.97 mm/min,利用系数提高0.815 t/(m^(2)·h),转鼓强度提高3.39%。预造球烧结中,由于难制粒精矿的分离,常规制粒料部分的制粒性能得到优化,局部碱度得到提高,形成大量的针柱状铁酸钙。在常规制粒料与球团料交界处固相固结与液相固结同时存在,铁酸钙与铁氧化物相互交织,形成球团嵌入式分布的成品矿结构,具有良好的成矿效果和强度性能。

参杞强精颗粒成型工艺优化与稳定性研究

目的探讨参杞强精颗粒成型工艺优化方案,并考察其成品稳定性。方法采用单因素试验考察湿法制粒工艺。以浸膏粉与辅料的配比(A)、乙醇浓度(B)、润湿剂用量(C)为主要影响因素,以吸湿率、溶化率、成型率、休止角为评价指标,采用L9(34)正交试验法优选参杞强精颗粒成型工艺。同时,考察参杞强精颗粒的长期稳定性和加速稳定性。结果正交试验法优选的最佳成型工艺为浸膏粉与辅料配比为1∶1,乙醇浓度为65%,0.3%甜菊素的颗粒口感较好,润湿剂用量为15~20 mL,生产环境的相对湿度应控制在70%以下。在稳定性考察过程中加速试验和长期试验均符合规定。结论优化后的成型工艺方法科学合理,稳定可行,操作简便,所制得颗粒符合各项指标的相关规定,且稳定性好,可为参杞强精颗粒的生产及其后续研究开发提供实验依据。

基于正交实验优化中药配方颗粒调剂工艺

目的:探讨影响中药配方颗粒药品下药量因素,优化最佳配药、储存条件,保证患者用药安全、有效,提高患者对中药配方颗粒药品的满意度。方法:通过正交实验法优化最佳配药、储存条件,对中药配方颗粒进行质量监管。结果:配方颗粒调剂工艺的影响因素依次为:湿度>粒径>温度;最佳调剂工艺为温度21℃,湿度45%,粒径为全部通过2号筛且不通过3号筛。结论:温度、湿度、粒径三者对配方颗粒的调剂工艺都有显著影响,依据本实验所得最佳配药条件,能达到最准确配药量。

大亳菊总黄酮的提取及其颗粒剂制备工艺研究

优选大亳菊总黄酮的提取及其颗粒剂制备工艺。采用正交试验,以总黄酮提取率为判断标准,优选大亳菊总黄酮的提取工艺;以成型率为判断标准,优选大亳菊总黄酮颗粒剂的制备工艺。结果表明,优选的大亳菊总黄酮提取工艺为:液料比为25∶1,乙醇体积分数75%,提取温度85℃,回流时间1.25h;优选的制粒工艺为:可溶性淀粉∶糊精=1∶1,浸膏粉∶辅料=1∶3,干燥温度60℃,干燥时间2h。该工艺简便、稳定,可以用于大亳菊总黄酮的提取及其颗粒剂的制备。

3种中药配方颗粒全生产链的污染微生物考察

目的:对郁金、桑叶、蝉蜕中药配方颗粒生产全过程污染微生物进行考察,建立数据库,探索中药配方颗粒生产过程微生物关键控制点及控制措施,为企业提供示范性研究,为制定标准、改进生产工艺提供依据,填补质量全过程控制的空白。方法:对3种中药配方颗粒的原材料、中间产品、成品按照《中国药典》2020年版进行分析检测,采用质谱技术对负载微生物进行鉴定,分析研究从药材原料到中药配方颗粒成品的外源性污染微生物的程度及容易污染微生物的种类。结果:3种中药配方颗粒的原材料(中药饮片)微生物污染较严重,原材料的耐热芽孢杆菌即使经过工艺处理后,仍能在中间产品、成品中检出,并造成部分批次需氧菌总数结果超出限度规定;中间产品、成品中还检出来源于人和动物肠道中的屎肠球菌。结论:①加强中药饮片的微生物污染控制,有利于降低终端产品的微生物负载;②3种中药配方颗粒的生产工艺存在芽孢类微生物污染的风险,需优化生产工艺参数来降低微生物负载;③药品生产企业需加强对产品全过程控制,降低微生物污染风险。

苏葶宣肺颗粒的制备工艺及初步药效研究

目的优选苏葶宣肺颗粒的最佳提取工艺和成型工艺,并探讨其对气管平滑肌的作用。方法采用L9(34)正交设计实验法,以迷迭香酸和黄芩苷的含量以及浸膏得率为指标,考察提取次数、提取时间和加水倍量对苏葶宣肺颗粒提取工艺的影响,优选苏葶宣肺颗粒的最佳提取工艺。以制粒情况、成型率、吸湿率、休止角及溶解度为评价指标,对辅料种类和药辅比例等因素进行考察,确定最佳制剂成型工艺。制备大鼠离体气管环后浸泡于K-H液,采用BL-420S生物机能系统测定其张力变化,分别观察苏葶宣肺颗粒对大鼠正常离体气管和磷酸组胺(His)、乙酰胆碱(ACh)致痉的大鼠离体气管张力的影响,计算解痉率。结果苏葶宣肺颗粒的最佳提取工艺为:加10倍量水,浸泡30 min,提取2次,每次提取60 min。3批正交验证实验综合评分均数为92.07,RSD为0.51%。最佳成型工艺为:浸膏、糊精、淀粉按3∶2.5∶4的比例制成软材,用10目筛网制成颗粒。苏葶宣肺颗粒对大鼠正常离体气管平滑肌具有舒张作用,对ACh和His致大鼠离体气管平滑肌收缩均有一定的解痉作用。结论本文建立了苏葶宣肺颗粒稳定可行的制备工艺,为后续的研发、质量控制奠定了基础。苏葶宣肺颗粒对离体气管平滑肌有舒张作用,其机制可能与抗组胺和抑制胆碱受体有关。

软坚散结颗粒制备工艺及其质量标准建立

目的 建立软坚散结颗粒制备工艺及其质量标准。方法 优化挥发油包合工艺和颗粒成型工艺,确定颗粒制备工艺。TLC法定性鉴别玄参、浙贝母、莪术、麸炒白术,HPLC法测定哈巴苷、哈巴俄苷、贝母素甲、贝母素乙的含量。结果 最佳包合工艺为挥发油与β-环糊精比例1∶10,包合时间120 min,包合温度45℃;最优成型工艺为按药辅比1∶0.8混入可溶性淀粉,90%乙醇润湿,制粒。TLC斑点清晰,阴性无干扰。哈巴苷、哈巴俄苷、贝母素甲、贝母素乙在各自范围内线性关系良好(r≥0.999 4),平均加样回收率105.63%~110.87%,RSD 2.9%~5.6%。结论 软坚散结颗粒制备工艺稳定可行,并且该制剂质量标准专属性强,重复性好,可用于其质量控制。

不同APP添加量对复合肥料造粒性能的影响

聚磷酸铵(APP)作为近几年备受关注的新型肥料,在农业应用中研究较多且效果显著,但作为原料在复合肥料生产中的研究报道较少。为探究APP与其他肥料的复配和造粒性能,采用APP、磷酸一铵(MAP)、磷酸二铵(DAP)等原料通过复配再造粒制备复合肥料。肥料制备共设计两个方案,其中方案I以APP、MAP、尿素和K_(2)SO_(4)为原料,方案II以APP、DAP、尿素和K_(2)SO_(4)为原料,同时两个方案又分别设定不同的APP添加量作为变量,且对原料配伍性能、造粒过程现象、加水量、成粒率、肥料p H、颗粒强度、颗粒分散性及肥料吸湿性等造粒性能进行了评价。结果表明:APP与其他原料复配再造粒能够制备2~4.75 mm的颗粒产品;当聚合磷质量分数≥40%时,复配性能良好;不同磷源配伍对复合肥料造粒性能有明显影响,方案II的产品成粒率、颗粒强度和分散性均优于方案I,但方案II的吸湿性较强;适宜的APP添加量有利于复合肥料造粒,两个方案均显示在聚合磷质量分数为20%~40%时,肥料产品的成粒率较高,方案I>67%,方案II>77%。

正交试验优选壮药龙路通颗粒提取工艺研究

目的:优选壮药龙路通颗粒提取工艺。方法:用高效液相色谱法测定三七皂苷R_(1),人参皂苷Rg_(1)和Rb_(1),并以出膏率、三七皂苷R_(1),人参皂苷Rg_(1)和Rb_(1)含量为评价指标。采用单因素法考察加水量、提取时间和提取次数,并通过正交试验优选壮药龙路通颗粒最佳提取工艺。结果:以三七皂苷R_(1),人参皂苷Rg_(1)和Rb_(1)的含量作为龙路通颗粒质控标准,测得龙路通颗粒中3种指标性成分的质量分数分别为三七皂苷R_(1)45.6~60.6 mg/g,人参皂苷Rg_(1)159.3~234.4 mg/g,和人参皂苷Rb_(1)143.8~246.0 mg/g;龙路通颗粒最佳提取工艺为加水煎煮提取3次,第一次加12倍量水,第二、三次分别加10倍量水,每次1.5 h。结论:优选的提取工艺合理可行,为壮药龙路通颗粒的生产及进一步开发提供了实验依据。

基于UHPLC-Q-TOF-MS/MS技术的百蕊颗粒入血成分研究

采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOF-MS/MS)技术辨析百蕊颗粒灌胃大鼠后的原型成分和代谢产物,并研究其主要体内代谢过程。大鼠口服给药百蕊颗粒后,采用UHPLC-Q-TOF-MS/MS技术采集血清样本数据,正、负离子模式下同时扫描,结合前期体外化学成分质谱数据以及提取各化学成分的精确质荷比等信息对百蕊颗粒在大鼠体内的原型成分和代谢产物进行辨识研究。结果在大鼠体内中共检测到20个原型成分和10个代谢产物,其中原型成分包括生物碱类化合物6个,黄酮类化合物4个,有机酸类3个等其他化合物,主要代谢途径包括还原反应和水解反应、硫酸化反应和葡萄糖醛酸结合反应。该研究为揭示百蕊颗粒药效物质基础奠定了基础,也为其中成药的开发与利用提供应用价值。