基于近红外光谱法的阿托伐他汀钙片质量一致性评价及含量快速测定

目的：建立近红外光谱法对阿托伐他汀钙片进行质量一致性评价及有效含量的快速测定。方法：采用便携式近红外光谱仪,采集23批阿托伐他汀钙片样品的漫反射近红外光谱数据,使用主成分分析（principal component analysis,PCA）建立不同批次阿托伐他汀钙片样品的质量一致性评价模型。使用不同光谱预处理方法对原始光谱进行光谱预处理,采用组合区间偏最小二乘（synergy interval partial least squares,SiPLS）算法对建模波数区间进行优化,并以高效液相色谱（high performance liquid chromatography,HPLC）法为参考方法,建立阿托伐他汀钙片的近红外定量分析模型。结果：使用不同批次阿托伐他汀钙片的光谱信息建立的PCA模型分类效果良好。对不同的光谱预处理方法进行比较,得到光程散射校正（multiplicative scattering correction,MSC）为最佳光谱预处理方法。当全光谱划分为30个区间时,选择3个子区间进行组合可得到最佳建模波数范围。校正模型的交叉验证均方根误差（root mean square error of cross-validation,RMSECV）为1.230 2,交叉验证相关系数（correlation coefficient of cross-validation,R_CV）为0.914 6,预测模型的预测均方根误差（root mean square error of prediction,RMSEP）为1.676 4,预测相关系数（correlation coefficient of the prediction,R_P）为0.964 2。结论：该研究建立的定性和定量方法准确、可靠,可以快速进行阿托伐他汀钙片的质量一致性评价及含量测定。     

近红外光谱技术快速测定杞菊地黄丸中马钱苷的含量

目的应用近红外光谱技术建立杞菊地黄丸(浓缩丸)中马钱苷含量的快速测定方法。方法以HPLC法测定样品中马钱苷的含量作为参考值,同时使用近红外漫反射光谱技术,采集113份杞菊地黄丸样品的近红外漫反射光谱,利用偏最小二乘法,建立马钱苷含量的快速测定模型。结果建立的校正模型的相关系数和内部交叉验证均方差分别为0.998 8和0.093 4;经外部验证,模型的预测相关系数r和预测均方差分别为0.986 7和0.084 9。结论该方法操作简便,结果准确、可靠,可用于杞菊地黄丸中马钱苷含量的快速测定。     

Application of diffuse reflectance near-infrared spectroscopy for determination of crystallinity

Studies were conducted to investigate the use of near-infrared spectroscopy (NIRS) for determining degree of crystallinity. Physical mixtures of amorphous/crystalline indomethacin and amorphous/crystalline sucrose were prepared over several composition ranges. Spectra were obtained on powder samples contained in glass vials using diffuse reflectance sampling. Parallel studies were conducted using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) for comparison. NIRS standard curves were constructed by plotting crystalline weight percent against the ratio of responses at two wavelengths or by partial least squares regression. NIRS standard curves demonstrated higher coefficients of determination and lower standard errors than either XRPD or DSC. Validation standards confirmed the accuracy of NIRS over XRPD. Method error analysis demonstrated comparable accuracy for NIRS and XRPD, with NIRS showing slightly better precision in repeated crystallinity determinations for a 50% crystalline sucrose sample. Interpretive analysis of the NIRS spectra was performed using neutron scattering and polarized Raman spectroscopy data obtained from the literature. Results indicated that the NIRS differences between crystalline and amorphous sucrose may be attributed to the disruption of regular vibrational modes when crystalline sucrose is rendered amorphous.     

Low-level determination of polymorph composition in physical mixtures by near-infrared reflectance spectroscopy

Near-infrared reflectance spectroscopy (NIRS) was employed to quantify sulfathiazole (STZ) forms I and III in binary physical mixtures in which one form was the dominant component. Physical mixtures of the polymorph pair were made by weight, ranging from 0 to 5% STZ form I mixed with STZ form III, and near-infrared spectra of the powder samples contained in glass vials were obtained over the wavelength region of 1100 to 2500 nm. A calibration plot was constructed by plotting STZ form I weight percent against a ratio of second-derivative values of log (1/R') (where R' is the relative reflectance) versus wavelength. The coefficients of determination, R(2), were > 0.9983 and standard errors were low for these calibration models. The instrument reproducibility, method error, and limits of detection (LOD) and quantification (LOQ) of the method were assessed. The LOD and LOQ were determined from the standard deviation of the response of the 0% analyte sample (0% STZ form I containing 100% STZ form III). The LOQ was subsequently validated with independently prepared samples. The results show that polymorphs can be quantified in binary physical mixtures in the 0.3% polymorph composition range. These studies indicate that NIRS is a precise and accurate quantitative tool for determination of polymorphs in the solid state, is comparable to other characterization techniques, and is more convenient to use than many other methods.     

Nondestructive determination of the ambroxol content in tablets by Raman spectroscopy

We describe a method for determining the ambroxol content in tablets nondestructively. To obtain a reliable quantitative calibration, we prepared 20 pellet samples (ambroxol content: 8.30-16.25 wt.%) and acquired their Raman spectra while rotating the pellets. The spectra of the rotated samples reflected the compositional variations better than those that were recorded without rotation. To reduce both the baseline variations and the spectral noise simultaneously, the spectra were pre-processed using wavelet transformation (WT). Then, we used the normalization method before partial least-squares (PLS) regression to correct Raman intensity variation from laser power fluctuation. The achieved standard error of cross validation (SECV) was 0.30%. Two different datasets where Raman intensity was artificially changed were prepared and the corresponding spectra were quantitatively analyzed. The result was reproducible even if laser intensity was fairly changed. Additionally, two different commercial tablets were analyzed and the accuracy of measurement was better for a tablet that had the similar spectral features of the standard pellet samples. The proposed method can be utilized for the analysis of commercial tablets if standard tablets of various ambroxol concentrations that have the same chemical components including additives and the same physical shape of tablets are available.     

Cross-linked high amylose starch derivatives for drug release. II. Swelling properties and mechanistic study

Acetate (Ac-), aminoethyl (AE-), and carboxymethyl (CM-) high amylose starch cross-linked 6 (HASCL-6) derivatives were previously shown to control the release of drugs over 20 h from monolithic tablets highly loaded (up to 60% drug). This report describes the swelling characteristics, which allow a better understanding of the mechanisms involved in the control of the drug release from the said polymeric matrices. The tablet swelling of HASCL-6, Ac-HASCL-6, and AE-HASCL-6 was found to not be affected by the ionic strength and by the pH between 1.2 (gastric) and 7 (intestinal), whereas the swelling of CM-HASCL-6 was shown to depend on both ionic strength and pH of the release medium. For all the studied polymers the drug loading did not change the equilibrium swelling ratio but affected the initial swelling velocity, seemingly due to the competition between drug and polymer for water uptake, a phenomenon probably influenced by the loading and the drug solubility. It was also shown that the increase of ionic strength would slightly increase the drug release time probably by decreasing the amount of free water still available to solubilize the drug present into the matrix.     

NIR transmission spectroscopy for rapid determination of lipid and lyoprotector content in liposomal vaccine adjuvant system CAF01

It is of crucial importance to determine the concentration of the different components in the formulation accurately, during production. In this respect, near-infrared (NIR) spectroscopy represents an intriguing alternative that offers rapid, non-invasive and non-destructive sample analysis. This method, combined with multivariate data analysis was successfully applied to quantify the total concentration of lipids in the liposomal CAF01 adjuvant, composed of the cationic surfactant dimethyldioctadecylammonium bromide (DDA) and the immunomodulator α,α′-trehalose 6,6′-dibehenate (TDB). The near-infrared (NIR) detection method was compared to a validated high-performance liquid chromatography (HPLC) method and a differential scanning calorimetry (DSC) analysis, and a blinded study with three different sample concentrations was performed, showing that there was no significant difference in the accuracy of the three methods. However, the NIR and DSC methods were more precise than the HPLC method. Also, with the NIR method it was possible to differentiate between various concentrations of trehalose added as cryo-/lyoprotector. These studies therefore suggest that NIR can be used for real-time process control analysis in the production of CAF01 liposomes.     

Integration of SIMCA and near-infrared spectroscopy for rapid and precise identification of herbal medicines

The recognition, control, and monitoring of herbal medicinal materials is a crucial work and challenge in the pharmaceutical industry. Consequently, the development of a rapid and accurate inspection method and model is an important goal and job. The raw materials of a variety of herbal medicines were measured using nondestructive near-infrared spectroscopy with soft independent modeling of class analogy to build up the classification model. The adulterated samples could be eliminated by the analysis of the model, and identification rates were demonstrated in the range of 98–100%. The method could be applied not only to the pharmaceutical industry but also to the food industry. Food materials can be measured with the inspection model for effective identification and determination of adulteration.     

Cross-linked high amylose starch derivatives for drug release III. Diffusion properties

Acetate (Ac-), aminoethyl (AE-) and carboxymethyl (CM-) derivatives of cross-linked high amylose starch (HASCL-6) were previously shown to control the release of drugs over 20 h from highly loaded (up to 60% drug) monolithic tablets. This report presents a diffusion analysis, aimed to facilitate a better understanding of the mechanisms involved in the control of the drug release from these hydrogels. The diffusion was found to depend on the molecular weight of the diffusant, whereas the partition coefficient depended on the affinities of the diffusant for the polymers and for the dissolution media via attractive or repulsive ionic interactions. The diffusion was also affected by the swelling of CM-HASCL-6, which, unexpectedly, increased with the decrease of the ionic strength. This diffusion analysis completes the swelling studies of HASCL-6 and of its derivatives, allowing the prediction of release kinetics of various active agents.     

拉曼光谱法快速测定盐酸异丙嗪注射液的含量

目的:建立拉曼光谱法快速测定盐酸异丙嗪注射液的含量。方法:采用智能激光拉曼光谱仪扫描样品,激发波长780 nm,激光强度100 MW,光圈25 μm,光栅400 gr·mm^-1,分辨率2.0 cm^-1,曝光时间50 s,曝光次数2次,扫描范围100~3 200 cm^-1。结果:盐酸异丙嗪在20~200 mg·ml^-1范围内与拉曼定量峰面积呈良好的线性关系(r=0.998 2),平均加标回收率为98.13%,RSD为1.05%(n=9)。结论:本方法快速、简单、可靠,可用于盐酸异丙嗪注射液的含量测定。     

高效液相色谱法快捷测定黄原胶中 D-甘露糖含量的探究

目的建立高效液相色谱 -示差折光( HPLC-RID)法测定黄原胶中 D-甘露糖含量的方法。方法该研究起止时间为 2022年 6月至 2023年 3月。选择 Phenomenex Rezex RCM-Monosaccharide Ca(+300 mm×7.80 mm,8 μm)色谱柱,以双蒸水为流动相,流速: 0.4 mL/min,柱温: 75 ℃,进样量: 20 μL,检测器为示差折光检测器( RID)。结果色谱图显示 D-甘露糖分离度良好, D-甘露糖在 20.09~100.46 μg范围内与峰面积线性关系良好( r=0.999 6)D-甘露糖平均加样回收率为 99.10%,相对标准偏差( RSD)为 0.81%(n=6),精密度、稳定性、重复性试验的 RSD均小于 2%。结论,所建立的 D-甘露糖含量测定方法可靠,操作简便,专属性强,重复性好,适合黄原胶中 D-甘露糖的含量测定,为黄原胶食用以及药用产品的进一步开发提供了参考数据。     

Near-infrared FT-Raman spectroscopy as a rapid analytical tool for the determination of diltiazem hydrochloride in tablets.

This study was performed to develop a fast and reliable analytical method for the quantitative determination of diltiazem hydrochloride in tablets. HPLC is currently the preferred method, but is time consuming due to extensive sample preparation. FT-Raman spectroscopy was used to quantitatively analyse diltiazem hydrochloride in commercially available tablets (Tildiem) and in experimental tablets prepared at lab-scale. The percentage of diltiazem hydrochloride in each tablet was determined by calculating-after vector normalisation-the total peak area of the spectral band between 1625 and 1560 cm(-1). No spectral interference from tablet excipients was seen at this spectral band. After FT-Raman spectroscopy the same samples were analyzed based on the HPLC method described in the USP XXIV. The drug dosage per tablet obtained from the vibrational spectroscopy method correlated well with the results obtained using HPLC analysis for both the commercial tablets (HPLC: 63.57+/-0.13 mg; Raman: 63.28+/-0.26 mg (n=50)) and the experimental tablets (HPLC: 181.02+/-0.25 mg; Raman: 181.22+/-0.35 mg (n=50)). FT-Raman is a reliable alternative for the HPLC method to quantify the amount of diltiazem hydrochloride in tablets. The spectroscopic method is faster because it eliminates sample pre-treatment. Furthermore the FT-Raman method has an additional advantage of not requiring solvents.     

近红外光谱法快速测定丹参醇沉过程中的鞣质

目的:建立一种运用近红外光谱技术快速测定丹参注射液醇沉工艺过程中鞣质浓度的方法。方法:以磷钼钨酸-干酪素法为对照分析方法,比较了不同的光谱预处理方法对校正结果的影响,运用偏最小二乘回归法建立了丹参醇沉液近红外光谱图与鞣质浓度对照值之间的校正模型,并对模型的预测能力进行验证。结果:光谱经过一阶导数和Savitzky-Golay卷积平滑法处理,选取5430～5839cm-1波段建模得到的定量校正模型效果最好,校正模型的相关系数r达到0.964,预测集预测误差均方根(RMSEP)为1.43g.L-1。结论:本方法操作简便、快速无损,可发展成为中药醇沉过程的一种过程分析方法。     

近红外光谱分析技术在线测定颈痛颗粒流化床制粒过程中的水分

目的 利用近红外光谱分析技术快速测定颈痛颗粒流化床生产过程中水分的含量。方法 以颈痛颗粒为研究对象,对流化床生产设备的视窗进行改造,采用Micro NIR PAT-U对生产过程进行在线监测,利用偏最小二乘法建立颈痛颗粒流化床生产过程中水分的定量分析模型。结果 最终建立的水分含量PLS定量模型RMSEC,RMSECV,RMSEP, R2c,R2cv,R2p分别为0.245 4%、0.287 1%、0.279 8%、0.909 1、0.880 6、0.904 6,外部验证的平均相对误差为3.0%。结论 近红外光谱分析技术可以替代水分测定仪,对颈痛颗粒流化床生产过程中水分的含量进行在线、快速、准确地测定。     

维生素B2片快速检验的近红外漫反射光谱法定量模型初探

目的初步建立近红外漫反射光纤光谱法测定维生素B2片含量的定量模型。方法利用＂药品快检车＂配备的近红外光谱仪,用光纤探头采集近红外漫反射光纤光谱,对国内不同生产企业的维生素B2片样品建立了定量分析模型。应用最小二乘法（PLS）,在7 116.4~4 468.5 cm-1范围内,光谱采用一阶导数与多元散射校正（MSC）预处理,建立回归校正模型。结果维生素B2在57.5~87.5 mg.g-1的浓度范围内,定量分析模型的相关系数R2为0.9378,内部交叉验证均方差（RMSECV）为1.79,预测均方差（RMSEP）为1.36。结论近红外漫反射光纤光谱法能够实现维生素B2片的无损定量分析,可用于快速筛查。     

阿奇霉素颗粒剂近红外通用性定量分析模型的建立(英文)

用近红外漫反射光谱法建立了阿奇霉素颗粒剂的通用性定量分析模型。以21个厂家的103批阿奇霉素颗粒剂建立模型,其浓度范围为3.0%至24.5%。对模型进行外部验证,均方根差(RMSEP)为0.613。此外,还参照ICH的指导原则对模型进行方法学验证,验证项目有:专属性、线性、准确度和精密度。可见,通过选择合适的训练集样本,并精心的挑选建模谱段,建立阿奇霉素颗粒剂的近红外通用性定量分析模型是可行的,该模型可用于快速分析国内各厂家产品的含量。     

应用色度仪法快速测定药用辅料蔗糖色值的可行性研究

目的：建立测定蔗糖色值的方法。方法：采用紫外-可见光分光光度仪,以4 cm比色皿于420 nm处测定溶液的吸光度,以公式计算蔗糖溶液色值;采用色度仪,校准后测定不同色号的黄色标准比色液及蔗糖溶液颜色反射率值（CIE Y 值）,并将溶液颜色反射率值折算为黄色色号;通过直线回归分析,对33批蔗糖开展研究,并对所得数据结果间的相关性进行分析,考察应用色度仪法快速测定蔗糖色值的可行性。结果：测定的33批蔗糖色值结果在13 IU~223 IU之间,溶液颜色反射率值（CIE Y 值）在85%~92%之间,折算的黄色色号在0~22之间;经回归分析,色值测定结果与色度仪法测定的溶液颜色反射率值结果的回归方程斜率P值小于0.000 1,色值测定结果及溶液黄色色号结果的回归方程斜率P值小于0.000 1,颜色反射率值与色值、色值与溶液颜色均具有较强的相关性。结论：应用色度仪法对蔗糖色值开展快速准确地测定具有可行性,同时,也进一步为改进《中国药典》标准方法提供了技术支持。     

Application of near-infrared spectroscopy to the determination of the sites of manufacture of proprietary products

Reflectance near-infrared (NIR) spectroscopy has been investigated as a method to distinguish between the sites of manufacture of a number of proprietary tablets. As test samples, parallel imports which are pharmaceutically equivalent products manufactured at different sites have been used. Three products: Aremis/Besitran^®, Renitec^® and Voltarol Retard^® originating from two or more sites and Adalat^® from a single site were examined. The principal component analysis (PCA) score plots showed that spectra of tablets originating from different sites of manufacture often gave rise to statistically different populations. PCA loadings indicated that the differences were related to moisture content and excipients. Spectra were used to construct a library for the classification of tablets to predict the site of manufacture based on the method of residual variance of the principal components. Where a large data set was available (Aremis/Besitran^® tablets) prediction rates for the successful identification of the two sites of manufacture, Madrid and Barcelona, were 95.7 and 98.1%, respectively for the validation set with all errors encountered of Type I.     

Approach to the determination of hydrate form conversions of drug compounds and solid dosage forms by near-infrared spectroscopy

Near-infrared (IR) spectroscopy is used for the rapid, nondestructive identification and quantitation of the hydrate form of drug compounds forming both single and multiple hydration states. Near-IR is shown to be useful in both bulk drug and in finished solid dosage forms. The capability of near-IR to nondestructively analyze samples allows the kinetics of hydrate form conversions to be measured directly in formulated products. In addition, the environmental conditions for stability of the individual hydration states are mapped out using near-IR spectroscopy. Detailed molecular mechanisms are given to account for the near-IR spectral changes that occur upon hydration. The technique is applied in both laboratory studies as well as in a process environment for at-line analysis of active pharmaceutical ingredient hydration state during pharmaceutical processing.     

Determination of film-coated tablet parameters by near-infrared spectroscopy

Near-infrared (near-IR) spectroscopy was used in the determination of three parameters of theophylline tablets film-coated with ethylcellulose. Spectra of individual intact tablets were collected on two near-IR spectrometers: a grating-based spectrometer, and an acousto-optic tunable filter spectrometer. Calibrations were developed for the prediction of the time to 50% dissolution (t_50%) of theophylline for tablets of varying coat thickness, for the determination of the thickness of the ethylcellulose coat applied, and for the prediction of the hardness of coated tablets. Principal component analysis was performed on the spectra prior to calibration development. The standard errors of calibration (SEC) and prediction (SEP) for determination of dissolution rates were 2.8 and 6.6 min, respectively. The SEC for the coating thickness calibration was 0.0002 inches, with an SEP of 0.00024 inches, and the SEC and SEP for the determination of tablet hardness were 0.54 and 0.62 kilopons, respectively.