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.     

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.     

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.     

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。     

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。     

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.     

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。     

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.     

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.     

近红外光谱快速鉴别左炔诺孕酮片的真伪

目的应用近红外光谱快速鉴别左炔诺孕酮片的真伪。方法对12批样品分别采集近红外光谱,用于建立左炔诺孕酮片鉴别比对模型,并用经高效液相色谱验证的4批样品检验模型的准确度。结果所建立方法对验证集4批样品可准确判别。结论该法简便、快速、无损和准确,可在药品检测车上推广应用。     

近红外光谱技术在投料放行阶段疗效物质基础快速评价的研究进展

通过对近红外光谱分析技术在药用原辅料正确性快速评价方面应用的总结,分析近红外光谱分析技术分析速度快、无损失等特点,推动其在投料放行阶段疗效物质基础快速评价方面的应用,提高药品质量一致性。近红外光谱分析技术既可以实现原辅料进厂及车间投料放行的快速鉴别,也可以对原辅料理化性质及药品成分含量进行检测,从而确保药物物质基础正确,提高药品质量一致性。     

复杂体系SiO_2的快速测定

本文采用重量法对复杂体系中 SiO_2的测定进行了研究,建立快速,准确的方便分析系统。     

近红外光谱法快速测定罗布麻叶中总黄酮含量

目的建立罗布麻叶中总黄酮含量近红外光谱定量分析模型,快速测定罗布麻叶中总黄酮含量。方法采集并用多种预处理近红外光谱,结合偏最小二乘法(PLS),建立罗布麻叶中总黄酮含量的定量分析模型并对所建立的模型进行优化。结果优化后定量模型的校正集预测值与测定值之间的相关系数RC为0.979 6,校正集标准差(SEC)为0.21,验证集标准差(SEP)为0.13、交互检验验证集标准差(SECV)为0.27。结论该定量模型具有较高的预测效果,建立的方法可快速定量分析罗布麻叶中总黄酮含量。