In-line solid state prediction during pharmaceutical hot-melt extrusion in a 12 mm twin screw extruder using Raman spectroscopy

The aim of this research was to use Raman spectroscopy for the in-line monitoring of the solid state of materials during pharmaceutical hot-melt extrusion in the die head of a 12 mm (development scale) twin-screw extruder during formulation development.A full factorial (mixed) design was generated to determine the influence of variations in concentration of Celecoxib (CEL) in Eudragit® E PO, three different screw configurations and varying barrel temperature profiles on the solid state, ‘melt temperature’ and die pressure of continuously produced extrudates in real-time. Off-line XRD and DSC analysis were used to evaluate the suitability of Raman spectroscopy for solid state predictions. First, principal component analysis (PCA) was performed on all in-line collected Raman spectra from the experimental design. The resulting PC 1 versus PC 2 scores plot showed clustering according to solid state of the extrudates, and two classes, one class where crystalline CEL is still present and a second class where no crystalline CEL was detected, were found. Then, a soft independent modelling of class analogy (SIMCA) model was developed, by modelling these two classes separately by disjoint PCA models. These two separate PCA models were then used for the classification of new produced extrudates and allowed distinction between glassy solid solutions of CEL and crystalline dispersions of CEL. All extrudates were classified similarly by Raman spectroscopy, XRD and DSC measurements, with exception of the extrudates with a 30% CEL concentration extruded at 130 °C. The Raman spectra of these experiments showed bands which were sharper than the amorphous spectra, but broader than the crystalline spectra, indicating the presence of CEL that has dissolved into the matrix and CEL in its crystalline state. XRD and DSC measurements did not detect this. Modifications in the screw configuration did not affect the solid state and did not have an effect on the solid state prediction of new produced extrudates.Secondly, the influence of variations in die pressure on the Raman spectra was examined. The applied drug concentration, processing temperature and feeder performance influence the die pressure, which is reflected in the Raman spectra as a change in spectral intensity. When applying PCA on the raw spectra from the experimental design, the first principal component describes the influence of die pressure on the spectra, which was seen as a decrease in Raman intensity of the whole spectrum when the pressure in the sample increased. Clustering according to processing temperature was found, although the temperature in the die remained constant, indicating that a difference in viscosity, resulting in a changed die pressure, was detected. When the feeder was stopped, the score values of the first principal component almost simultaneously decreased, and only stabilized once the die pressure became stable. Since Raman spectra collected in the extrusion die are influenced by changes in die pressure, disturbances upstream of the extrusion process can be observed and identified in the Raman measurements.     

近红外光谱法快速鉴别市售不同厂家生产的藿胆丸

目的:建立快速鉴别市售不同厂家生产的藿胆丸的方法。方法:采用近红外光谱法。采集7个厂家的藿胆丸样品的近红外光谱,并用判别分析方法和聚类分析方法分别对数据进行分析。结果:聚类分析中,当类间距离为0.64时,K厂家和G厂家样品首先聚为一类,当类间距离为1.84时,其他5个厂家样品自成一类;所建立的判别分析模型错判例数为0,判别分析准确率为100%。结论:所建立的近红外光谱法可以快速、准确、无损地对不同厂家生产的藿胆丸制剂进行定性分析。     

近红外光谱法快速分析小儿复方磺胺甲嗯唑颗粒的水分含量

目的利用近红外漫反射光谱（NIRDRS）分析技术和化学计量学方法对小儿复方磺胺甲嗯唑颗粒的水分含量进行快速定量分析。方法以全国不同企业生产的小儿复方磺胺甲嗯唑颗粒为分析对象,为扩大检测的浓度范围,通过恒温恒湿引湿的方法制得实验室制备样品,用光纤探头直接接触样品采集近红外漫反射光谱,采用偏最小二乘法（PLS）建立模型。结果小儿复方磺胺甲嗯唑颗粒水分定量分析模型由64个样本经内部交叉验证建立,42个样本用于外部验证,浓度范围为0．12％～6．15％,内部交叉验证相关系数（r）为0．9975,交叉验证均方差（RMSECV）为0．0835,外部验证均方差（RMSEP）为0．0865。结论建立的定量分析模型能对小儿复方磺胺甲嚷唑颗粒的水分含量进行准确、快速定量分析,方法简单可靠,可用于药品的现场快速分析。     

利用NIR技术建立阿莫西林克拉维酸钾颗粒一致性比对模型的研究

目的：应用近红外漫反射技术建立阿莫西林克拉维酸钾颗粒一致性检验模型快检方法。方法：收集阿莫西林克拉维酸钾颗粒的近红外漫反射光谱,运用OPUS软件建立一致性检验模型,并采用三台仪器对模型进行交叉验证。结果：模型通过仪器交叉验证,利用该一致性检验模型能无损伤、快速、准确地判断阿莫西林克拉维酸钾颗粒的真伪。结论：该方法快速简便,结果准确,适用于假劣药品的快速筛查。     

TLC-SERS联用法检测降糖中成药中添加的格列类药品

目的：研究降糖中成药中非法添加格列类药品的表面增强拉曼光谱（ surface enhanced Raman spectroscopy , SERS）检测方法。方法利用薄层色谱法将待检成分与中药基质进行简单分离,采用表面增强拉曼光谱技术对薄层板上的微量物质进行检测。通过摸索模拟阳性样品中格列类药品的SERS检测条件,建立可用于降糖中成药中非法添加物的检测方法。结果采用有机溶剂DMF制备所得的银溶胶可以获得较好的格列类药物SERS图谱。结论该研究所建立的TLC与SERS联用方法检测简便、快速、经济,可用于降糖中成药中非法添加格列类药品的快速检测。     

近红外光谱法快速鉴别不同厂家的天王补心丸（大蜜丸）

目的：建立天王补心丸（大蜜丸）的近红外一致性检验模型,为其不同厂家鉴定提供科学依据。方法：使用MPA型近红外光谱仪（1.5 m光纤探头）、OPUS 5.5软件,分别采用二阶导数＋矢量归一化法和一阶导数法对其平均光谱进行预处理。结果：采用一阶导数预处理方法,CI值设为4.4时,所建模型能够将不同厂家的天王补心丸（大蜜丸）快速鉴别出来。结论：此方法方便、快捷、不破坏样品,能够作为不同厂家天王补心丸（大蜜丸）的快速分类鉴别方法。     

Thermal Stability and Decomposition Kinetics of 1-Alkyl-2,3-Dimethylimidazolium Nitrate Ionic Liquids: TGA and DFT Study

The thermal stability and decomposition kinetics analysis of 1-alkyl-2,3-dimethylimidazole nitrate ionic liquids with different alkyl chains (ethyl, butyl, hexyl, octyl and decyl) were investigated by using isothermal and nonisothermal thermogravimetric analysis combined with thermoanalytical kinetics calculations (Kissinger, Friedman and Flynn-Wall-Ozawa) and density functional theory (DFT) calculations. Isothermal experiments were performed in a nitrogen atmosphere at 240, 250, 260 and 270 °C. In addition, the nonisothermal experiments were carried out in nitrogen and air atmospheres from 30 to 600 °C with heating rates of 5, 10, 15, 20 and 25 °C/min. The results of two heating modes, three activation energy calculations and density functional theory calculations consistently showed that the thermal stability of 1-alkyl-2,3-dimethylimidazolium nitrate ionic liquids decreases with the increasing length of the alkyl chain of the substituent on the cation, and then the thermal hazard increases. This study could provide some guidance for the safety design and use of imidazolium nitrate ionic liquids for engineering.     

Study of the Solid-State Synthesis of Nickel Ferrite (NiFe2O4) by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Raman Spectroscopy

Spinel ferrite compounds continue to receive a lot of attention due to their unique properties. Among the numerous synthesis routes existing, the solid-state method was applied for the production of nickel ferrite, by introducing the use of a quartz vial. A mixture of nickel oxide (NiO) and hematite (Fe₂O₃) was ground and vacuum-sealed in the vial and different thermal treatment programs were tested. The resulting particles were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy. For temperatures, below 1000 °C, the solid-state reaction is not complete as nickel oxide (NiO) and hematite (Fe₂O₃) are still present. The reaction time is a decisive parameter for the morphology of the particles obtained. If, for different reaction times, the particle size distribution is always between 0.3 and 1.7 µm, a longer reaction time leads to the formation of dense, interconnected clusters of particles. Optimal parameters to synthesize a pure phase of spherical nickel ferrite were sought and found to be a reaction temperature of 1000 °C for 72 h.     

Electrical Property Analysis of Textured Ferroelectric Polycrystalline Antimony Sulfoiodide Using Complex Impedance Spectroscopy

Antimony sulfoiodide (SbSI) is a ferroelectric semiconductor with many interesting physical properties (optical, photoconductive, ferroelectric, piezoelectric, etc.). The electrical properties of textured polycrystalline SbSI obtained by the rapid cooling of a melted mass in liquid nitrogen are presented in this work using ac impedance spectroscopy over a wide temperature range (275–500 K) in the frequency range of 1 Hz to 100 kHz. Detailed studies of the impedance Z*(ω), conductivity σ*(ω), electric modulus M*(ω), and dielectric permittivity ε*(ω) of this material were performed using complex impedance spectroscopy for the first time. This study showed that the impedance and related parameters are strongly dependent on temperature. The internal domain structure and the presence of grain boundaries in textured polycrystalline SbSI explain the obtained results.     

Steryl Sinapate as a New Antioxidant to Improve Rapeseed Oil Quality during Accelerated Shelf Life

In recent years, steryl esters have become an attractive for the cosmetic, pharmaceutical, and food industries. Hence, the effect of exogenous antioxidant, β-sitosteryl sinapate on oxidative stability and antioxidant activity (AA) of refined rapeseed oil was evaluated by the accelerated shelf-life test. Oxidative parameters of refined rapeseed oil—peroxide value (PV), anisidine value (p-AnV), acid value (AV), and spectrophotometric indices (K₂₃₂, K₂₆₈)—increased during storage. However, the addition of β-sitosteryl sinapate caused a decrease of the primary and secondary oxidation products in the supplemented oils in comparison with the control sample. Moreover, oils with steryl ester had higher AA than oil without the synthetic antioxidant. The accelerated storage negatively affected the antioxidant potential of refined and enriched oils causing the AA decrease by 25–54% and 7–15%, respectively. Studies have consistently demonstrated beneficial associations between the presence of β-sitosteryl sinapate in oil samples and the inhibition of their oxidative degradation under the accelerated conditions. Additionally, the possibility of using the synchronous fluorescence (SF) spectroscopy and excitation–emission matrix (EEM) fluorescence spectroscopy for identification and observing changes in main fluorescent components present in non-supplemented and supplemented rapeseed oils during the accelerated storage was attempted.