DoE

DoE
  • 文章类型: Journal Article
    这项研究提供了三种不同型号的摩托车发动机的翅片传热研究结果。这项研究的目的是使外部温度最小化,因为当传热速率最大化时,将找到最佳设计。该研究获得了由于对流传热和风冷翅片设计引起的外边界温度之间的平衡。传热系数根据风速(Km/hr)和努塞尔数而变化。分析是在三种不同的发动机模型上进行的,名为A,B和C。优化设计是通过仿真设计的B,具有较低的温度增益,较低的变形和较低的法向应力。DOE(实验设计)对发动机的优化设计进行了三个参数的鳍片厚度,鳍的大小,和鳍的形状,并根据DOE病例再次进行分析。用于制造模型的材料是具有200W/mK的热导率的铝合金6061。通过采取750℃的外边界温度对设计的模型进行了研究。在40Km/h的速度下,传热系数约为77.28W/m2K。
    This research presents the results of a fin heat transfer study of three different models of the motorcycle engine. The objective of this study is to minimize the external body temperature because the optimum design will be found when the heat transfer rate is maximized. The study obtains the procurement of a balance between the outer boundary temperature due to convective heat transfer and air-cooled fin design. Heat transfer coefficient varies according to wind velocity (Km/hr) and Nusselt Number. The analysis was performed on three different engine models, named A, B and C. The optimum design was design B through simulation which has lower temperature gain, lower deformation and lower normal stress. DOE (Design of Experiments) was performed on the optimum design of the engine among all with three parameters thickness of fin, size of fin, and shape of fin, and again analysis was performed according to DOE cases. The material used for manufacturing the models was aluminum alloy 6061 which has a thermal conductivity of 200 W/mK. The study was performed on the designed models by taking the outer boundary temperature of 750oC. The heat transfer coefficient was about 77.28 W/m2K at 40 Km/h velocity.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    效力测定的快速发展对于挽救生命的疫苗的发展至关重要。传统的噬斑测定或百分之五十的组织培养感染剂量(TCID50)测定用于测量活病毒疫苗的效力是耗时的,劳动密集型,低吞吐量和高可变性。这里描述的是两种呼吸道病毒感染疫苗的基于细胞的报告效力测定的开发和鉴定,一种基于重组水泡性口炎病毒(rVSV)骨架,在本文中称为疫苗1,另一个基于麻疹病毒媒介,称为疫苗2。报告效力测定使用经过改造以组成型表达NanuLuc®荧光素酶的VeroE6细胞系,称为VeroE6-NLuc或JM-1细胞系。活病毒感染JM-1细胞,如rVSV或麻疹病毒,引起细胞病变效应(CPE)并将NanuLuc®从细胞质释放到上清液中,其数量反映了病毒感染的强度。通过在对数-对数线性模型中使用平行线分析(PLA)与参考标准进行比较来计算相对效力。报告分析显示出良好的线性,准确度,和精度,因此适用于疫苗效力测定。对疫苗1报告物测定的进一步评估证明了对所选择的测定参数的一系列故意变化以及与噬斑测定的相关性的稳健性。总之,我们已经证明,使用JM-1细胞系的报告基因试验可用作支持多种活病毒疫苗生产和释放的效价试验.
    The rapid development of potency assays is critical in the development of life-saving vaccines. The traditional plaque assay or fifty percent tissue culture infectious dose (TCID50) assay used to measure the potency of live virus vaccines is time consuming, labor intensive, low throughput and with high variability. Described here is the development and qualification of a cell-based reporter potency assay for two vaccines for respiratory viral infection, one based on the recombinant vesicular stomatitis virus (rVSV) backbone, termed Vaccine 1 in this paper, and the other based on the measles virus vector, termed Vaccine 2. The reporter potency assay used a Vero E6 cell line engineered to constitutively express NanuLuc® luciferase, termed the VeroE6-NLuc or JM-1 cell line. Infection of JM-1 cells by a live virus, such as rVSV or measles virus, causes a cytopathic effect (CPE) and release of NanuLuc® from the cytoplasm into the supernatant, the amount of which reflects the intensity of the viral infection. The relative potency was calculated by comparison to a reference standard using parallel line analysis (PLA) in a log-log linear model. The reporter assay demonstrated good linearity, accuracy, and precision, and is therefore suitable for a vaccine potency assay. Further evaluation of the Vaccine 1 reporter assay demonstrated the robustness to a range of deliberate variation of the selected assay parameters and correlation with the plaque assay. In conclusion, we have demonstrated that the reporter assay using the JM-1 cell line could be used as a potency assay to support the manufacturing and release of multiple live virus vaccines.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    磨损是切削刀具的一个重要问题,特别是当由于硬质矿物骨料颗粒的存在而碾磨沥青混凝土时。由切削材料施加在切削刀具上的压力和所产生的切削力直接影响刀具磨损。要估算沥青铣削中的切削力,作者建议使用实验室实验或具有成本效益的离散元方法(DEM)建模-通过模拟真实条件-作为在真实条件下的直接测量是具有挑战性的。本文介绍了旨在确定沥青路面铣削过程中切削力的原始实验程序的结果。一个专门的支架配备了一个移动板和记录装置的设计,以改变铣削深度,转速,和前进的速度。将水平力值的实验结果与DEM建模的数值结果进行了比较。发现增加铣削深度和前进速度都会导致更高的切削力。一般来说,DEM建模趋势与实验结果一致,虽然DEM值通常较高。统计分析允许将铣削深度识别为影响切削力的最重要参数,并确定铣削参数的最佳组合,以实现作用在切削齿上的最小水平力。即,15毫米的铣削深度和190毫米/分钟的先进速度。
    Abrasion wear is a significant concern for cutting tools, particularly when milling asphalt concrete due to the presence of hard mineral aggregate particles. The pressure exerted on the cutting tool by the chipped material and the resulting cutting forces directly influence tool wear. To estimate the cutting forces in asphalt milling, the authors propose using either laboratory experiments or cost-effective Discrete Element Method (DEM) modeling-by simulating the real conditions-as direct measurement under real conditions is challenging. This article presents results from an original experimental program aimed at determining the cutting forces during asphalt pavement milling. A specialized stand equipped with a moving plate and recording devices was designed to vary milling depth, rotational speed, and advance speed. The experimental results for horizontal force values were compared with numerical results from DEM modeling. It was found that both increasing the milling depth and the advance speed lead to higher cutting forces. Generally, DEM modeling trends align with experimental results, although DEM values are generally higher. The statistical analysis allowed identification of the milling depth as the most significant parameter influencing cutting force and the optimal combination of milling parameters to achieve minimum horizontal force acting on cutting tooth, namely, 15 mm milling depth and 190 mm/min advanced speed.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    Mitapivat是一部小说,2022年由美国食品和药物管理局批准用于治疗溶血性贫血的一流口服活性丙酮酸激酶激活剂。没有关于mitapivat降解杂质的鉴定的文献。本研究涉及mitapivat在各种胁迫条件下的降解行为,例如水解,光解,热,和氧化应激。多变量分析发现,自变量,也就是说,摩尔浓度,温度,和时间,彼此相互作用以影响mitapivat的降解。一个具体的,准确,并开发了精确的高效液相色谱(HPLC)方法来从其降解产物中分离mitapivat。在C-18柱(250mm×4.6mm×5µm)上使用0.1%甲酸缓冲液和乙腈的组合进行梯度洗脱。该方法按照国际人用药品技术要求协调理事会Q2(R2)指南进行验证。采用LC-电喷雾电离-四极杆-飞行时间来鉴定降解产物。基于串联质谱和准确的质量测量,总共鉴定了七种新型的米塔皮伐降解产物。通过DEREK毒性预测工具对mitapivat及其降解产物的硅内毒性进行了定性评估。
    Mitapivat is a novel, first-in-class orally active pyruvate kinase activator approved by the US Food and Drug Administration in 2022 for the treatment of hemolytic anemia. There is no literature available regarding the identification of degradation impurities of mitapivat. The present study deals with the degradation behavior of mitapivat under various stress conditions such as hydrolytic, photolytic, thermal, and oxidative stress. The multivariate analysis found that the independent variables, that is, molarity, temperature, and time, are interacting with each other to affect the degradation of mitapivat. A specific, accurate, and precise high-performance liquid chromatographic (HPLC) method was developed to separate mitapivat from its degradation products. The separation was achieved on the C-18 column (250 mm × 4.6 mm × 5 µm) using the combination of 0.1% formic acid buffer and acetonitrile in gradient elution profile. The method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Q2(R2) guideline. LC-electrospray ionization-Quadrupole-time of flight was employed to identify degradation products. A total of seven novel degradation products of mitapivat were identified based on tandem mass spectrometry and accurate mass measurement. In-silico toxicity of mitapivat and its degradation products was qualitatively evaluated by the DEREK toxicity prediction tool.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    Heck反应被广泛用于构建各种生物相关支架,并已成功用于生产活性药物成分(API)。通常,与末端烯烃的反应对反式取代的烯烃产物具有较高的产率和立体选择性,和原始协议的许多绿色变体已被开发用于此类底物。然而,这些方法可能无法以相同的效率应用于具有挑战性底物的反应,如内烯烃,提供三取代的烯烃。在目前的工作中,我们在绿色条件下实施了Heck反应方案,以获得三取代的烯烃作为最终产物或具有药物意义的关键中间体。对模型反应进行的一组初步实验导致基于实验设计(DoE)研究选择简单且绿色的设置。以这样的方式,最佳实验条件(催化剂负载量,烯烃的等价物,碱和四烷基铵盐,composition,和溶剂的量)已经确定。然后,进行了第二组实验,使反应完成并考虑其他因素。如此定义的方案涉及使用EtOH作为溶剂,微波(MW)辐射以实现短反应时间,和负载型催化剂PdEnCat®40,它提供了更容易的回收和再利用。在不同的芳基溴化物和内部烯烃上测试这些条件以评估底物范围。此外,为了尽可能限制废物的产生,开发了一种简单的异构化程序,将异构副产物转化为所需的共轭烯烃,这也是热力学上最受欢迎的产品。本文公开的方法代表绿色,高效,和易于使用的处理对不同的三取代的烯烃通过Heck反应。
    The Heck reaction is widely employed to build a variety of biologically relevant scaffolds and has been successfully implemented in the production of active pharmaceutical ingredients (APIs). Typically, the reaction with terminal alkenes gives high yields and stereoselectivity toward the trans-substituted alkenes product, and many green variants of the original protocol have been developed for such substrates. However, these methodologies may not be applied with the same efficiency to reactions with challenging substrates, such as internal olefins, providing trisubstituted alkenes. In the present work, we have implemented a Heck reaction protocol under green conditions to access trisubstituted alkenes as final products or key intermediates of pharmaceutical interest. A set of preliminary experiments performed on a model reaction led to selecting a simple and green setup based on a design of experiments (DoE) study. In such a way, the best experimental conditions (catalyst loading, equivalents of alkene, base and tetraalkylammonium salt, composition, and amount of solvent) have been identified. Then, a second set of experiments were performed, bringing the reaction to completion and considering additional factors. The protocol thus defined involves using EtOH as the solvent, microwave (mw) irradiation to achieve short reaction times, and the supported catalyst Pd EnCat®40, which affords an easier recovery and reuse. These conditions were tested on different aryl bromides and internal olefines to evaluate the substrate scope. Furthermore, with the aim to limit as much as possible the production of waste, a simple isomerization procedure was developed to convert the isomeric byproducts into the desired conjugated E alkene, which is also the thermodynamically favoured product. The approach herein disclosed represents a green, efficient, and easy-to-use handle towards different trisubstituted alkenes via the Heck reaction.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    体外转录(IVT)反应是RNA聚合酶催化从DNA模板产生信使RNA(mRNA),以及mRNA原料药生产过程中商品成本最高的单元操作。为了降低mRNA生产的成本,试剂应得到最佳利用。由于催化,IVT反应的多组分性质,优化是一个多因素问题,非常适合用于优化和识别设计空间的实验设计方法。我们推导了IVT反应的数据驱动模型,并探索了驱动过程产量的因素(以g/L为单位),包括核苷三磷酸(NTP)浓度和Mg:NTP比对反应产率的影响,以及如何优化主要成本驱动因素RNA聚合酶和DNA模板,同时尽量减少dsRNA的形成,mRNA产品中的关键质量属性。我们报告了一种得出最佳反应设计的方法论方法,其中反应的成本效率提高了44%。我们证明了该模型对不同长度的mRNA构建体的有效性。最后,我们将IVT反应的产率最大化为24.9±1.5g/L,从而使有史以来报告的最高IVT产量翻了一番。
    In vitro transcription (IVT) reaction is an RNA polymerase-catalyzed production of messenger RNA (mRNA) from DNA template, and the unit operation with highest cost of goods in the mRNA drug substance production process. To decrease the cost of mRNA production, reagents should be optimally utilized. Due to the catalytic, multicomponent nature of the IVT reaction, optimization is a multi-factorial problem, ideally suited to design-of-experiment approach for optimization and identification of design space. We derived a data-driven model of the IVT reaction and explored factors that drive process yield (in g/L), including impact of nucleoside triphosphate (NTP) concentration and Mg:NTP ratio on reaction yield and how to optimize the main cost drivers RNA polymerase and DNA template, while minimizing dsRNA formation, a critical quality attribute in mRNA products. We report a methodological approach to derive an optimum reaction design, with which cost efficiency of the reaction was improved by 44%. We demonstrate the validity of the model on mRNA construct of different lengths. Finally, we maximized the yield of the IVT reaction to 24.9 ± 1.5 g/L in batch, thus doubling the highest ever reported IVT yield.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    这项研究采用了质量设计(QbD)方法来喷雾干燥由Soluplus®和微晶纤维素组成的无定形克霉唑纳米悬浮液(CLT-NS)。使用Box-Behnken设计,进行了系统的评估,以分析进口温度的影响,%抽吸,和进料速率对克霉唑喷雾干燥纳米悬浮液(CLT-SDNS)的关键质量属性(CQA)的影响。在这项研究中,采用回归分析和方差分析来检测显著因素和相互作用,能够开发喷雾干燥过程的预测模型。优化后,CLT-SD-NS使用X射线粉末衍射(XRPD)进行分析,傅里叶变换红外光谱(FTIR),动态扫描量热法(DSC),和体外溶出研究。结果显示了显著的变量,包括入口温度,进料速率,和吸入率,影响产量,再分散性指数(RDI),和最终产品的水分含量。为关键质量属性(CQA)创建的模型显示出统计学意义,p值为0.05。XRPD和DSC证实了CLT-SD-NS中CLT的非晶态,和FTIR表明CLT和赋形剂之间没有相互作用。在体外溶解研究中显示,CLT-SD-NS的溶解速率提高(在DI水中增加3.12倍,在pH7.2溶解介质下增加5.88倍),归于环状再分散纳米无定形CLT颗粒。利用实验设计(DoE)方法进行精心设计的研究。
    This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    使用聚合物纳米颗粒的siRNA的成功治疗性递送似乎是有希望但未被广泛理解和实现的复杂目标。尽管经过多年的研究,没有基于聚合物的递送系统被批准用于临床。聚合物,作为一个传递系统,表现出相当大的复杂性和可变性,使他们的一致生产是一项具有挑战性的努力。然而,更好地了解聚合物赋形剂的聚合过程可能会提高重现性和材料质量,从而更有效地用于药物产品。这里,我们提出了一种结合实验设计和Python脚本数据科学来建立预测模型,从中可以提取影响聚β-氨基酯(PBAE)合成结果的重要参数,临床前用于核酸递送的一种常见类型的聚合物。我们合成了一个由27个聚合物组成的库,使用正交中心复合材料(CCO-)设计,每个在不同的温度下具有不同的反应时间和离析物比率。该设计允许使用非常有限数量的实验来详细表征因子重要性和相互作用。我们通过1H-NMR分析所得组合物和GPC测量的尺寸分布来表征聚合物。为了进一步理解一锅法合成中嵌段聚合的复杂机理,我们开发了一个Python脚本,帮助我们理解可能的逐步增长步骤。我们成功开发并验证了预测响应面,并对基于多精胺的两亲性PBAE的合成有了更深入的了解。
    Successful therapeutic delivery of siRNA with polymeric nanoparticles seems to be a promising but not vastly understood and complicated goal to achieve. Despite years of research, no polymer-based delivery system has been approved for clinical use. Polymers, as a delivery system, exhibit considerable complexity and variability, making their consistent production a challenging endeavor. However, a better understanding of the polymerization process of polymer excipients may improve the reproducibility and material quality for more efficient use in drug products. Here, we present a combination of Design of Experiment and Python-scripted data science to establish a prediction model, from which important parameters can be extracted that influence the synthesis results of polybeta-amino esters (PBAEs), a common type of polymer used preclinically for nucleic acid delivery. We synthesized a library of 27 polymers, each one at different temperatures with different reaction times and educt ratios using an orthogonal central composite (CCO-) design. This design allowed a detailed characterization of factor importance and interactions using a very limited number of experiments. We characterized the polymers by analyzing the resulting composition by 1H-NMR and the size distribution by GPC measurements. To further understand the complex mechanism of block polymerization in a one-pot synthesis, we developed a Python script that helps us to understand possible step-growth steps. We successfully developed and validated a predictive response surface and gathered a deeper understanding of the synthesis of polyspermine-based amphiphilic PBAEs.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:干细胞衍生疗法具有治疗再生临床适应症的潜力。静态培养具有有限的放大能力,因此限制了其使用。悬浮培养可用于大量生产靶细胞,但也提出了与压力和聚集稳定性相关的挑战。
    方法:在垂直轮式生物反应器中利用实验设计(DoE)方法,我们评估了具有多种特性的介质添加剂。评估的添加剂是肝素钠盐(HS),聚乙二醇(PEG),聚乙烯醇(PVA),PluronicF68和硫酸葡聚糖(DS)。选择多个响应变量来评估细胞生长,响应于添加剂输入的多能性维持和聚集体稳定性,和数学模型被生成和调整为最大预测能力。
    结果:在19种不同的培养基组合上使用100ml立式轮生物反应器测定4天扩增iPSC,从而产生可以优化多能性的模型,稳定性,和扩张。扩展优化导致了PA的组合,PVA和PEG与E8。该混合物导致比单独的E8短40%的膨胀倍增时间。多能性优化器强调了向E8培养基中添加1%PEG的重要性。使3D培养中的聚集体融合最小化的聚集体稳定性优化表明肝素和PEG两者的相互作用可以限制聚集以及增加hiPSC的维持能力和扩增。表明控制融合是扩展和维护的关键参数。在生物反应器中以40RPM的速度降低的两种细胞系上验证优化的解决方案,显示了对具有高频率的OCT4和S0X2的多能性标记物(>90%)的聚集体的一致性和延长的控制。在优化培养基中作为团块传代后,维持约1-1.4天的倍增时间。控制聚集体融合允许生物反应器速度降低,因此在大规模扩增中施加在细胞上的剪切应力降低。
    结论:本研究控制了悬浮培养物中的聚集体大小,同时告知iPSC状态的伴随状态控制。这种方法的更广泛的应用可以解决培养基优化复杂性和生物反应器放大的挑战。
    BACKGROUND: Stem cell-derived therapies hold the potential for treatment of regenerative clinical indications. Static culture has a limited ability to scale up thus restricting its use. Suspension culturing can be used to produce target cells in large quantities, but also presents challenges related to stress and aggregation stability.
    METHODS: Utilizing a design of experiments (DoE) approach in vertical wheel bioreactors, we evaluated media additives that have versatile properties. The additives evaluated are Heparin sodium salt (HS), polyethylene glycol (PEG), poly (vinyl alcohol) (PVA), Pluronic F68 and dextran sulfate (DS). Multiple response variables were chosen to assess cell growth, pluripotency maintenance and aggregate stability in response to the additive inputs, and mathematical models were generated and tuned for maximal predictive power.
    RESULTS: Expansion of iPSCs using 100 ml vertical wheel bioreactor assay for 4 days on 19 different media combinations resulted in models that can optimize pluripotency, stability, and expansion. The expansion optimization resulted in the combination of PA, PVA and PEG with E8. This mixture resulted in an expansion doubling time that was 40% shorter than that of E8 alone. Pluripotency optimizer highlighted the importance of adding 1% PEG to the E8 medium. Aggregate stability optimization that minimizes aggregate fusion in 3D culture indicated that the interaction of both Heparin and PEG can limit aggregation as well as increase the maintenance capacity and expansion of hiPSCs, suggesting that controlling fusion is a critical parameter for expansion and maintenance. Validation of optimized solution on two cell lines in bioreactors with decreased speed of 40 RPM, showed consistency and prolonged control over aggregates that have high frequency of pluripotency markers of OCT4 and SOX2 (> 90%). A doubling time of around 1-1.4 days was maintained after passaging as clumps in the optimized medium. Controlling aggregate fusion allowed for a decrease in bioreactor speed and therefore shear stress exerted on the cells in a large-scale expansion.
    CONCLUSIONS: This study resulted in a control of aggregate size within suspension cultures, while informing about concomitant state control of the iPSC state. Wider application of this approach can address media optimization complexity and bioreactor scale-up challenges.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    Bedaquiline(BQ)固体脂质纳米粒(SLN),以前已经配制用于肠胃外给药,有患者不遵守结核病治疗的风险。这项研究提出了一种策略来开发BQSLN口服给药,以提高患者的依从性。制剂赋形剂的上限和下限水平由筛选实验产生。使用4个输入因子(BQ,卵磷脂,吐温80和PEG),来自3×2x2×2实验的全因子设计随机排列以研究3个响应变量:粒度分布(PSD),多分散指数(PdI),和zeta电位(ZP)。高剪切均化用于混合溶剂和水相,15%蔗糖作为冷冻保护剂。使用ζ分析仪评估响应变量,而TEM显微照片证实PSD数据。使用粉末X射线衍射和扫描电子显微镜(SEM)成像进行固态评估。使用对比的体外评估来确定等效剂量的BQ游离基粉和BQ-SLN的药物释放,两者都包装在硬明胶胶囊中。超声处理的制剂对PSD获得了显著的影响,PdI,ZP。p值(PdI为0.0001,在超声处理的配方中,作为自变量的BQ为0.0091)明显高于未超声处理的配方(PdI为0.1336,0.0117用于PSD)。SEM图像在100-400nm之间,描绘了嵌入脂质基质中的BQ纳米晶体。与药物的游离碱相比,SLN制剂提供更高的药物水平;从溶出曲线估计相似因子(f2=18.3)。
    Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug\'s free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号