近红外光谱技术用于血必净注射液提取过程的在线检测研究

目的:采用近红外透射光谱法,建立血必净注射液提取过程各质控指标的快速定量分析模型,并进行提取终点的快速判断,实现提取过程的在线检测。方法:以川芎、丹参和当归3种药材混合提取过程为例,采用偏最小二乘法回归(PLSR)分别建立阿魏酸浓度和含固量的定量校正模型,并将模型应用于提取过程的在线检测。使用移动块标准偏差(MBSD)算法实现对提取终点的快速判断。此外,采用模型更新方法,扩充原有模型,提高模型的稳定性和预测精度。结果:所建立的阿魏酸和含固量校正模型相关系数均达到0.986,采用所建模型进行在线分析,预测结果与实际测定值相关系数均大于0.967,预测相对偏差(RSEP)小于10%,相对分析误差(RPD)大于3。同时,MBSD算法的终点判断结果与实际相符。此外,将新的样品加入原校正模型进行模型更新后预测效果有所改善。结论:研究结果表明,利用近红外光谱技术可以实现提取过程中阿魏酸浓度和含固量的快速检测,并可快速判断提取终点。另外,模型更新方法有利于解决因药材质量、工况等发生变化导致的"模型失效"问题,从而扩展模型的使用范围。     

近红外光谱技术对女贞子进行快速检测方法的研究

目的:通过近红外光谱技术建立女贞子的快速检测鉴别真伪及产地的方法。方法:利用近红外漫反射光谱技术,按中国药典2015年版一部相关标准,以女贞子中水分及特女贞苷含量为参考值,建立女贞子中水分及特女贞苷定量模型,对女贞子进行快速含量测定;建立女贞子一致性检验模型,进行快速真伪鉴定及产地鉴别。结果:建立女贞子中特女贞苷含量与女贞子水分校正模型校正集的相关系数分别为95.15%,97.3%,校正集的内部交叉验证均方差(RMSECV)分别为0.364,0.161;预测值与实测值相差较小,能较准确地测定女贞子中特女贞苷的含量与女贞子水分。建立对女贞子定性鉴别的一致性检验模型能较准确判别女贞子的产地。结论:利用近红外光谱对女贞子中特女贞苷与女贞子水分进行定量,不同产地进行定性的方法快速、简便、预测结果准确,可成为女贞子的快速检验方法。     

复方益肝灵片近红外光谱快检方法考察

摘 要 目的： 采用近红外光纤光谱技术对复方益肝灵片进行快速判断厂家归属以及快速检定其中水飞蓟素的含量。方法: 以全国6个企业生产的93批复方益肝灵片作为分析对象,建立聚类分析模型。光谱预处理方法为二阶导数和矢量归一化;平滑点：13;光谱范围：9 000～4 100 cm^-1;光谱之间距离采用欧氏距离,光谱和类之间距离采用方差平方和法（Ward’s算法）。同样以全国6个企业生产的93批复方益肝灵片作为分析对象,建立定量分析模型。光谱预处理方法为一阶导数加矢量归一化;平滑点：17;光谱范围：9 100～7 300 cm^-1和7 100～4 100 cm^-1;采用偏最小二乘法回归。结果: 聚类模型可以很好的区分训练集中的药品,在对作为测试集的30张光谱进行验证中全部判断正确。所建立的定量模型交叉验证均方根误差（RMSECV）为0.082 8,决定系数为97.98%,外部验证均方根误差（RMSEP）为0.044 1,r²为98.95%。结论: 该聚类方法和定量模型快速简便、准确可靠,可以满足药品现场快速检查的需要。     

AOTF近红外光谱技术在淫羊藿提取过程在线检测中的应用

目的：研究声光可调滤光器（AOTF）近红外光谱技术,以实现淫羊藿提取过程的在线检测。方法采用AOTF近红外光谱仪,在淫羊藿提取的生产过程中实时采集近红外光谱,实时取样,采用紫外分光光度法进行离线检测。通过一阶微分PLS算法建立校正模型,利用外部验证和内部验证的方法考察模型预测的准确性。结果分别对提取过程3次煎煮提取液总黄酮含量建立模型,其相关系数分别为0.9699、0.9811、0.9059,内部验证的平均偏差为-0.28%、-0.21%、1.43%,外部验证的平均偏差分别为-0.72%、-0.26%、3.54%。结论 AOTF近红外光谱技术可有效地应用于淫羊藿提取过程的在线检测和质量控制。     

硫酸羟氯喹颗粒水分近红外光谱在线定量模型的建立

目的 为实时检测硫酸羟氯喹颗粒在流化床干燥过程中的水分含量变化,建立颗粒水分的在线近红外光谱定量模型.方法 物料颗粒在流化床的干燥过程中,实时取样并用水分测定仪测量颗粒水分,采用多元散射校正(multiplicative signal correction,MSC)、一阶导数和Karl Norris平滑的光谱预处理方法...     

基于近红外光谱技术的清咽片简化模拟混合过程终点判断方法研究

本研究简化模拟了清咽片混合过程,采用近红外(NIR)光谱技术对不同粒径体系下混合物中原辅料的混合终点进行监测,探究了不同粒径对混合过程终点的影响。实验共设计5个具有粒径差异的混合批次,待每批样品混合完成后,采集终点物料的近红外光谱,并运用偏最小二乘回归(PLSR)方法分别建立桔梗、柯子、硼砂、寒水石、微晶纤维素5种原辅料含量的定量校正模型,将模型应用于3批存在粒径差异样品的混合终点判断,同时使用移动块标准偏差(MBSD)算法对混合终点进行定性判别。结果显示,粒径越小的组分其混匀所需时间越短,且模型预测准确度相对较高。此外, MBSD方法虽然方便快捷,无需建模,但终点判断结果不如PLSR方法准确。利用NIR光谱技术探究不同粒径物料对混合过程终点的影响,有助于实现对清咽片混合过程终点的精准判断。     

近红外光谱分析技术在白芍水提过程中的在线控制研究

采用近红外光谱技术研究一种参枝苓口服液白芍单提过程的在线分析技术。方法在实验室模拟生产基础上,采用ANTARIS II近红外光谱仪采集白芍水提中间体的近红外光谱并采用高效液相色谱法测定样品中芍药苷含量,通过偏最小二乘法(PLS)拟合光谱数据与液相数据,建立了白芍水提过程中芍药苷定量分析模型。结果研究结果显示采用经OSC结合mean center预处理处理光谱在全光谱范围内所建模型最佳,模型评价参数RMSEC、R2cal、R2val、LVs分别为0.080 5、0.968 4、0.920 6、4,模型结果良好。结论本实验为参枝苓口服液白芍水提过程在线监控提供一种新的方法,有利于提高产品芍药苷含量为产品稳定生产及产品质量提供保障。     

基于近红外光谱的疏血通注射液浸提过程总固体含量分析

目的 建立一种快速测定疏血通注射液浸提过程中总固体含量的近红外光谱法。方法 以水蛭和地龙2种药材浸提过程为例,采用偏最小二乘法(PLS)建立总固体含量的近红外光谱分析校正模型,实现对总固体含量的快速测定。结果 近红外光谱在一阶导数结合Karl Norris平滑滤波处理下,建模效果最佳。水蛭总固体含量校正集相关系数(R)为0.810 8,校正集和验证集预测误差均方根(RMSEC、RMSEP)分别为0.583和0.495,交叉验证误差均方根(RMSECV)为0.81,校正集和验证集相对偏差(RSEC、RSEP)分别为6.11%和5.25%;地龙总固体含量校正集R值为0.975 5,RMSEC和RMSEP分别为1.10和1.85,RMSECV为1.61,RSEC和RSEP分别为4.68%和7.80%。结论 近红外光谱可用于快速测定疏血通注射液浸提过程中总固体含量,有望推广应用于中药浸提过程的在线质量控制。     

五味子中五味子乙素提取工艺研究

目的 考察影响五味子中五味子乙素提取的因素。方法 采用正交试验法，以溶剂浓度、溶剂用量、回流时间和溶剂pH值为因素，以提取液中五味子乙素含量为指标，对影响因素进行研究。结果 优选出了五味子乙素的最佳提取条件。结论 提取五味子乙素的最佳条件为加5倍量85%的乙醇、调节pH值为5.5、回流提取2 h。     

近红外光谱分析方法在七叶皂苷钠快速检测中的应用研究

目的 利用近红外光谱分析技术建立一种七叶皂苷钠的快检方法,用于注射用七叶皂苷钠药品的含量测定。方法 应用OPUS软件对采集光谱进行优化处理,分别采用PLS算法和因子化算法,建立定量模型和定性模型。结果 定量模型相关系数达到0.9926,交叉验证均方根误差为0.253,在预测试验中,样品的预测值与真实测定值偏差均小于5%,能够准确预测七叶皂苷钠的含量。结论 本研究建立的定性模型可有效区分未参与建模的其他品种样品,为该药品的快检筛查提供参考。     

Quantitative Monitoring the Anti-Solvent Crystallization and Storage Process for Nandrolone by Near-Infrared Spectroscopy

A novel hydrate (S_H2O) of nandrolone was prepared by anti-solvent methods. The crystallization processes with 2 schemes (A and B) were monitored by in-line near-infrared (NIR) spectroscopy. The amounts of S_H2O in powder samples obtained by the anti-solvent crystallization and storage process were quantified by NIR combined with chemometrics methods. In-line NIR spectra from 4500 to 8000 cm^?1 were chosen to capture physicochemical changes during the whole crystallization process. The combination of the principal component results with offline characterization (scanning electron microscopy, powder X-ray diffraction, NIR) data showed that both schemes yielded high purity S_H2O products, but the crystallization speed of scheme B was significantly accelerated. It was demonstrated that in-line NIR spectroscopy combined with principal component analysis can be very useful to monitor in real time and control the anti-solvent crystallization process. Moreover, the solubility and the solid-state transformation of nandrolone under different storage conditions were investigated. The apparent solubility of S_H2O was 2.19-2.44 times of Form I, and S_H2O was relatively stable when stored at a high relative humidity and temperature below 25°C.     

Determination of Indomethacin Crystallinity in the Presence of Excipients Using Diffuse Reflectance Near-Infrared Spectroscopy

Studies were conducted to investigate the use of near-infrared spectroscopy for determining the crystallinity of indomethacin in multi-component physical mixtures. Three calibration sets of amorphous/crystalline indomethacin physical mixtures were prepared over the composition range of 0–100% crystallinity. Each of the three calibration sets was diluted step-wise with increasing amounts of a single excipient (Avicel, α-lactose monohydrate, or sodium chloride). Near-infrared spectra were obtained after each round of dilutions using diffuse reflectance sampling on samples contained in glass vials. After a second derivative transformation, standard curves were constructed by plotting percent indomethacin crystallinity against the ratio of responses at two wavelengths. At dilution levels up to 75% Avicel or lactose, the calibration models demonstrated high coefficients of determination and low standard errors. Dilution with sodium chloride did not produce comparable results and it was necessary to use partial least-squares regression to achieve a similar level of error. These findings were confirmed with separate validation sets. An investigation of instrument error showed that the impact of instrument variability on quantification generally increased as a function of the dilution level.     

In-Situ Near-Infrared Spectroscopy Monitoring of the Lyophilization Process

Purpose. The purpose of this work was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to monitor the freeze-drying process in-situ. Methods. The experiment was performed in a pilot-scale freeze-dryer, in which the NIRS probe was interfaced using a lead-through to the lyophilizer. Special equipment for the sample presentation was developed. NIRS measurements were made using a FT (Fourier transform)-NIR spectrometer fitted with a single fiber reflectance probe. Results. The physical changes, that is, freezing, sublimation, and desorption, generated significant spectral changes. There was good agreement between NIRS monitoring and product temperature monitoring about the freezing process and the transition from frozen solution to ice-free material. The NIRS monitoring also provided new information about the process that was not possible to detect with product temperature monitoring, such as the rate of the desorption process and the steady-state where the drying was complete. The NIRS monitoring yields significantly more information about the actual process and essentially explains the observed changes of the product temperature during the lyophilization process. Conclusions. NIRS monitoring is a viable tool for in-situ monitoring, both qualitatively and quantitatively. It can facilitate investigations of the drying process within a sample. The small volume monitored makes sample presentation very important.     

Near-Infrared Spectroscopic Monitoring of the Film Coating Process

Purpose. The purpose of this study was to investigate the potential of near-infrared (near-IR) spectroscopy for non-destructive at-line determination of the amount of polymer coat applied to tablet cores in a Wurster column. Methods. The effects of coating composition on the near-IR spectroscopic determination of ethylcellulose (Aquacoat ECD-30) or hydroxypropylmethylcellulose (HPMC)-based (Spectrablend) coating were evaluated, as were the performance of several chemometric techniques. Results. Tablets were coated with up to 30% ethylcellulose or 22% HPMC, and samples were pulled at regular intervals during each coating run. Near-IR reflectance spectra of the intact tablets were then collected. The spectra were preprocessed by multiplicative scatter correction (MSC) or second derivative (D2) calculations, and calibrations developed using either principal components (PCs) or multiple spectral wavelengths. The near-IR method provided predictions of film applied with standard errors of 1.07% w/w or less. Conclusions. Near-IR spectroscopy can be profitably employed in a rapid and non-destructive determination of the amount of polymer film applied to tablets, and offers a simple means to monitor the film coating process.     

基于近红外光谱技术的当归提取物混合工艺研究

目的采用近红外光谱技术(NIR)建立当归提取物混合物中当归挥发油β-环糊精包合物的定量模型,并用于优化当归提取物混合工艺。方法以当归挥发油β-环糊精包合物含量为真实值,运用偏最小二乘法(PLS)建立近红外光谱与当归挥发油β-环糊精包合物含量之间的定量校正模型,并对混合工艺进行优选。结果所建近红外光谱定量模型的相关系数(R2)为99.33%,交互验证误差均方根(RMSECV)为0.195,验证集平均预测回收率为98.53%,所建立的当归提取物测定模型预测能力较好;当归提取物混合物不同部位中挥发油β-环糊精包合物含量测定的RSD值分别为1.88%、1.15%、2.71%,均小于5.0%,当归提取物的混合工艺为:混合转速5 r·min^-1,混合时间25 min。结论近红外光谱技术可用于当归提取物混合工艺过程中产品的检测与评价。     

Evaluation of Risk and Benefit in the Implementation of Near-Infrared Spectroscopy for Monitoring of Lubricant Mixing

On-line near-infrared spectroscopy (NIRS) was used to monitor lubricant blending to ensure the quality of the final dosage form. A quantitative multivariate NIR model was developed using different lubricant concentration levels. Real-time model predictions correlated well with the expected lubricant concentration during blending, which allowed determination of blend quality. The significance of sensor location on the blender at different fill levels was evaluated. The capability of this application was further assessed by real-time study of blending dynamics under varying process conditions and raw material attributes. The response of the developed NIR method to sudden spikes in analyte concentration, changes in raw material attributes, and perturbations to standard mixing procedures was evaluated. This study allows an understanding of risk factors associated with the implemented technology, and its ability to accurately monitor the process events. Furthermore, it highlights the importance of proper selection of processing conditions and raw material attributes to improve process robustness.     

近红外漫反射光谱法定量分析注射用二乙酰氨乙酸乙二胺

目的建立近红外漫反射光谱分析技术定量测定注射用二乙酰氨乙酸乙二胺含量的方法。方法采用傅立叶变换近红外光谱仪和固体光纤探头，采用InGaAs检测器，在12 000～4 000 cm^-1范围内每份样品扫描64次，求平均值，通过偏最小二乘法建立模型，样品建模采用波段为7 482.5～5 041.1 cm^-1。结果定量分析模型对未知样品的预测均方差RMSEP为2.03，预测值与真实值的相关系数R为0.996 9，平均回收率为(100.85±0.29)%，方法精密度RSD为0.28%。结论用近红外漫反射光谱分析技术对注射用二乙酰氨乙酸乙二胺进行定量分析，结果准确可靠，方法简便快速，不需预处理，适合大量重复性样品的分析测定。     

近红外光谱双模型法快速判别雷公藤去皮减毒工艺的水平

目的：利用近红外光谱法和化学计量学分析软件,建立快速判别雷公藤真伪的一致性模型和雷公藤去皮减毒工艺水平的相关系数模型。方法：收集雷公藤切片和打粉样本的近红外漫反射光谱,运用OPUS软件分别建立其一致性模型和相关系数模型,并用非雷公藤样本及去皮减毒不完全样本进行验证。结果：基于近红外光谱法建立了快速判别雷公藤样本的近红外光谱双模型：可以快速、准确地判断被测样本是否为雷公藤;可以判断雷公藤样本的去皮减毒工艺水平。结论：该方法建立的近红外光谱双模型法易于操作、快速有效,可作为判断雷公藤去皮减毒工艺水平的快速筛查方法。     

注射用磷霉素钠近红外定量分析通用性模型的建立

摘 要 目的： 利用近红外光谱法,建立注射用磷霉素钠含量快速检定方法。方法: 采集注射用磷霉素钠的近红外（NIR）光谱,建立近红外定量模型。结果: 以矢量归一化和多元散射校正法对光谱进行预处理、选择谱段范围为11 995.8～7 428.9及6 734.6～5 454 cm^-1,回归方法为偏最小二乘法。结论: 该近红外定量分析模型可用于注射用磷霉素钠快速定量分析。     

黄芩提取工艺的优化

目的:优化黄芩提取的工艺条件.方法:采用正交实验设计法,以高效液相色谱法(HPLC)测定从黄芩药材中提出黄芩苷的量为考察指标,考察加水量(A)、煎煮时间(B)、煎煮次数(C)3个因素.结果:优化的黄芩提取条件为A2B3C3.结论:加8倍量水,每次1.5 h,煎煮3次,黄芩苷的收率可达到88.5%.