Near-Infrared and Fourier Transform Infrared Chemometric Methods for the Quantification of Crystalline Tacrolimus from Sustained-Release Amorphous Solid Dispersion

The objective of the present research was to study the feasibility of using near-infrared (NIR) and Fourier transform infrared (FTIR)-based chemometric models in quantifying crystalline and amorphous tacrolimus from its sustained-release amorphous solid dispersion (ASD). ASD contained ethyl cellulose, hydroxypropyl methyl cellulose, and lactose monohydrate as carriers, and amorphous form of tacrolimus in it was confirmed by X-ray powder diffraction. Crystalline physical mixture was mixed with ASD in various proportions to prepare sample matrices containing 0%–100% amorphous/crystalline tacrolimus. NIR and FTIR of the samples were recorded, and data were mathematically pretreated using multiple scattering correction, standard normal variate, or Savitzky–Golay before multivariate analysis, partial-least-square regression (PLSR), and principle component regression (PCR). The PLSR models were more accurate than PCR for NIR and FTIR data as indicated by low value of root-mean-squared error of prediction, standard error of prediction and bias, and high value of R². Additionally, NIR data-based models were more accurate and precise than FTIR data models. In conclusion, NIR chemometric models provide simple and fast method to quantitate crystalline tacrolimus in the ASD formulation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2376–2385, 2014     

Interaction Between Superoxide Dismutase and Dipalmitoylphosphotidylglycerol Bilayers: A Fourier Transform Infrared (FT-IR) Spectroscopic Study

Purpose. Superoxide dismutase (SOD), an antioxidant enzyme, converts peroxide radicals into hydrogen peroxide. Liposomes have been used as carriers for SOD to enhance its antioxidant effect. Our previous DSC study has suggested that SOD binding to dipalmitoylphosphatidylglycerol (DPPG) may protect lipid membranes against oxygen-mediated injury. We now present FT-IR studies on the effect of DPPG binding on the temperature-induced SOD folding-unfolding process. Methods. The FT-IR spectra of SOD in D₂O or DPPG membranes are measured as temperatures increase from 28° to 121°C at a rate of 0.5°C/ min. From the quantitative determination of the changes in the amide I band components of the Fourier self-deconvoluted spectra, the DPPG-induced changes of SOD secondary structure could be detected as a function of temperature. Results. We observe that the relative intensity of the SOD bands from 28°C to 77°C show graduate loss of -sheet distorted structure, loss of turns, and existence of an intermediate state around 50°C. Beginning at 80°C, changes are obtained in three temperature regions: (i) 80°C, (ii) 92°C, (iii) 109°C. The result suggests that SOD folding/unfolding transition involves mostly the relative changes within the regions of helix-like hydrogen bonding pattern, turn, twisted -bend and irregular structures. When SOD is bound to DPPG, the conformational changes shift to lower temperatures, indicating a reduction of SOD thermal stability. In addition, the gel to liquid crystalline phase transition temperature of DPPG increases from 42°C to 43.5°C. Conclusions. These results suggest that the thermal stability of SOD is reduced by DPPG binding. However, DPPG bilayer is stabilized by the presence of SOD.     

傅立叶变换红外光谱技术在生物技术领域中的应用

目的总结傅立叶变换红外光谱技术（FTIR）在生物技术领域中的应用与研究概况。方法以傅立叶变换红外光谱技术在生物技术领域的研究现状为依据,对该技术理论和应用现状进行分析与归纳。结果与结论通过理论与实例分析表明,目前傅立叶变换红外光谱技术在生物技术研究中得到普遍应用,同时,随着相关理论的发展与完善,该项技术在相关领域的应用将更趋广泛与深入。     

Introduction to Fourier Transform Infrared Spectroscopy and Applications in the Pharmaceutical Sciences

The applications of infrared spectroscopy to pharmaceutical sciences is small compared to the applications of infrared spectroscopy to the fields of chemistry, biology, and biochemistry. This is unfortunate because modern routine infrared spectrometers are excellent research tools that provide very high signal-to-noise, high resolution, and extensive data-manipulation computer software packages. This review summarizes basic principles of infrared spectrometers and the use of Fourier self-deconvolution.     

Screening of Heparin API by Near Infrared Reflectance and Raman Spectroscopy

Near infrared (NIR) reflectance and laser Raman spectra for a set of 69 heparin powder samples obtained from several foreign and domestic suppliers were measured. Both the NIR and Raman spectra of individual heparin API powder samples were correlated with sample compositions determined from response corrected relative peak areas of the capillary electropherograms of the samples using a partial least squares (PLS) regression model. Twenty-eight sample spectra were used to develop PLS models for the three major sample components; heparin, oversulfated chondroitin sulfate (OSCS) and glycosaminoglycans (GAGs). The PLS models were then used to successfully predict the compositions of 41 additional heparin samples. The success of these rapid, nondestructive technologies to identify contamination of heparin with OSCS demonstrates the potential of spectroscopy and chemometrics for screening of processed raw materials. These technologies are meant for screening purposes and not meant to replace either of the methods (capillary electrophoresis and NMR) currently required by USP and FDA. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3540–3547, 2009     

Evaluation of a Raman Chemometric Method for Detecting Protein Structural Conformational Changes in Solution

Raman scattering shows promise as a powerful routine tool, to determine both secondary and the smaller tertiary structural changes that precede aggregation in both solutions and solids. A method was developed utilizing principal component analysis (PCA) of Raman spectra for detection of small, but meaningful, pH induced changes in tertiary protein structure linked to aggregate formation using α-lactalbumin solutions as a model. The sample preparation and spectral parameters, were optimized for a bulk Raman probe. Analysis of large regions (600–1850 cm^?1) yielded principal component (PC) scores useful for semi-quantitative comparison of protein conformation between formulations. PC loadings corresponded to specific structural peaks known to change with solution pH. PCA of circular dichroism (CD) spectra of dilute solutions yielded similar results. Sucrose is a common formulation excipient with a Raman spectrum that overlaps many protein peaks. With sucrose in the protein solution, the ability of PCA to discern protein structural changes from the Raman spectra was somewhat reduced. Analysis of a more limited spectral region (1530–1780 cm^?1) with negligible sucrose spectral contribution improved the discrimination of protein conformational states. The new Raman method accurately distinguished differences in protein structure in concentrated solutions. The long-term goal is to explore Raman characterization as a routine monitoring tool of protein stability in both solution and solid states.     

Prediction Discrepancies for the Evaluation of Nonlinear Mixed-Effects Models

Reliable estimation methods for non-linear mixed-effects models are now available and, although these models are increasingly used, only a limited number of statistical developments for their evaluation have been reported. We develop a criterion and a test to evaluate nonlinear mixed-effects models based on the whole predictive distribution. For each observation, we define the prediction discrepancy (pd) as the percentile of the observation in the whole marginal predictive distribution under H₀. We propose to compute prediction discrepancies using Monte Carlo integration which does not require model approximation. If the model is valid, these pd should be uniformly distributed over [0, 1] which can be tested by a Kolmogorov–Smirnov test. In a simulation study based on a standard population pharmacokinetic model, we compare and show the interest of this criterion with respect to the one most frequently used to evaluate nonlinear mixed-effects models: standardized prediction errors (spe) which are evaluated using a first order approximation of the model. Trends in pd can also be evaluated via several plots to check for specific departures from the model     

江中健胃消食片近红外一致性检验模型的建立

目的 运用近红外(NIR)漫反射光谱法检验江中健胃消食片,打击市场上销售的假冒药品,保障人民用药安全有效.方法 通过收集标示为江中药业股份有限公司生产的59个批次样本以及标示为其他厂家的多批健胃消食片样品,经实验室检验后,扫描其近红外光谱,结合实验室的检测结果,运用布鲁克公司的OPUS软件,建立江中健胃消食片的一致性检验模型,并用新的样品来验证模型的准确性.结果 建立的模型预测的结果与实验室测定的结果完全一致.结论 本方法简便快捷,可以准确鉴别健胃消食片的真伪.     

Fourier Transform Infrared (FTIR) Spectrometry for the Assay of Polyhedral Boron Compounds in Plasma and Pharmaceutical Formulations

The determination of polyhedral boron compounds such as sodium borocaptate directly in blood plasma is described using FTIR with computed nonlinear background subtraction of the water absorption band. The procedure can be performed in less than 15 min to a sensitivity level of 5 ppm boron (at a signal/noise ratio of 2.5), which is satisfactory in the clinical application of such compounds in neutron capture therapy of cancer. For boron compounds with suitable organic solubility, extraction from plasma into carbon tetrachloride is described as an alternative approach not requiring computed subtraction and capable of achieving a sensitivity level of 1 ppm. Both the boron and the lipid content of liposome formulations containing the polyhedral boron compounds can be measured simultaneously by FTIR. After extraction into CHC1₃:CH₃OH (1:1) or dispersion in ethanol, the extracts are evaporated to dryness and redissolved in carbon tetrachloride for FTIR assay.     

The Qualitative and Quantitative Analysis of Chlorpropamide Polymorphic Mixtures by Near-Infrared Fourier Transform Raman Spectroscopy

We analyzed binary mixtures of polymorphs A and B of chlorpropamide ((l-[4-chlorobenzenesulphonyl]-3-propyl urea)) by near-infrared Fourier transform Raman spectroscopy (FTRS). The individual polymorphs were prepared and characterized by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) microscopy, and physical appearance. The FTR spectra of the two polymorphs showed distinct differences which result from "crystal splitting effects. A series of 13 different mixtures of polymorph A and B was prepared by geometric mixing and their FTR spectra statistically analysed by factor analysis programming. Predictions of the A/B polymorphic composition of mixtures were made and compared with the theoretical values. The results demonstrate that FTRS combined with factor analysis programming may be successfully applied to the in situ monitoring of the A/B polymorphic nature of a chlorpropamide sample.     

Chemometric Models for Quantification of Carbamazepine Anhydrous and Dihydrate Forms in the Formulation

Carbamazepine (CBZ) exists in anhydrous and dihydrate forms. These forms differ in their solubility, dissolution rate, and subsequently in their oral bioavailability. The objective of this study is to develop multivariate chemometric models for estimation of the low level of carbamazepine dihydrate (CBZ-DH) in the CBZ formulations containing excipients of the commercial formulation. The selected excipients were mixed in proportions to make sample matrices ranging from 0% to 50% CBZ-DH. Fourier transform infrared (FTIR), near infrared (NIR), and hyperspectral imaging data were mathematically pretreated before the development of partial least square and principal component analysis regression models. The developed partial least squares regression and principal component analysis models demonstrated predictability of CBZ and CBZ-DH by multiple scattering correction and standard normal variate processing methods. Among the spectroscopic techniques used the model performance parameters such as root-mean-square error, standard error, and bias were found to be low for NIR compared to FTIR. The treated data have shown better model fitting than without treatment, which was demonstrated by correlation coefficient of 0.9778, 0.9824, and 0.9852 for FTIR, NIR, and hyperspectral imaging, respectively. Furthermore, the predicted values were found to be very close to the selected low level of independent samples having 5% CBZ-DH in tablet formulation.     

应用近红外光谱和拉曼光谱建立主成分分析模式识别法鉴别不同厂家阿法骨化醇软胶囊

摘 要 目的：比较近红外光谱法和拉曼光谱法对不同厂家阿法骨化醇软胶囊进行模式识别的特点,建立定性模型,并对不同厂家的阿法骨化醇软胶囊进行分析鉴别。方法: 应用近红外光谱与拉曼光谱,首次采用主成分分析的模式识别方法,结合光谱信息分析处方工艺,对不同厂家的阿法骨化醇软胶囊进行近红外光谱和拉曼光谱分析。结果: 近红外光谱法与拉曼光谱法均能提取出阿法骨化醇软胶囊的光谱信息,并进行判别分析。制剂中不同着色剂的荧光效应的影响在拉曼光谱中体现出较大差异。据此,建立了拉曼光谱主成分分析判别模型,前三个主成分重构的三维图中,代表6个不同厂家来源的阿法骨化醇样品点各自聚集,相互区分,实现了正确判别。结论: 利用拉曼光谱与近红外光谱互补性,建立不同工艺的阿法骨化醇软胶囊的识别方法,可用于阿法骨化醇软胶囊工艺一致性的分析。     

不同产地两面针衰减全反射傅立叶红外光谱特征及其应用

目的 利用外光谱法对不同产地两面针进行了研究,探讨不同产地的两面针样品不同部位的光谱特征,为快速鉴定两面针样品提供依据.方法 采用衰减全反射傅立叶变换红外光谱法(ATR-FT-IR)分别对不同产地两面针主根和须根的内、外皮以及木部进行研究.结果 不同产地的两面针样品红外光谱存在差异,来自同一产地的两面针样品不同部位的红...     

不同产地两面针衰减全反射傅立叶红外光谱特征及其应用

目的利用外光谱法对不同产地两面针进行了研究,探讨不同产地的两面针样品不同部位的光谱特征,为快速鉴定两面针样品提供依据。方法采用衰减全反射傅立叶变换红外光谱法(ATR-FT-IR)分别对不同产地两面针主根和须根的内、外皮以及木部进行研究。结果不同产地的两面针样品红外光谱存在差异,来自同一产地的两面针样品不同部位的红外光谱也存在较大的差异。结论 ATR-FT-IR能快速、简便地鉴定不同产地的两面针药材。     

Pharmaceutical Evaluation of Carbamazepine Modifications: Comparative Study for Photostability of Carbamazepine Polymorphs by using Fourier-transformed Reflection-absorption Infrared Spectroscopy and Colorimetric Measurement

Abstract— The tablet surface was evaluated without physical damage by means of Fourier-transform infrared reflection-absorption spectroscopy (FT-IR-RAS) and colorimetric measurement (colour difference, AE) of the carbamazepine polymorphs I, II and III, after photodegradation at two irradiation intensities (30 and 120 J cm^?2 s ^?1) under a near-UV fluorescent lamp. The surface of sample pellets of all crystalline forms turned gradually from white to yellow-orange upon exposure to light, and the discoloration rate of form II was faster than that of forms I and III, indicating that form II was the most unstable of the three. The major photoproducts were identified by HPLC, NMR and MS analyses. The carbamazepine content on the surface of the tablet was determined based on the absorption at 1685 cm^?1 atributable to C = O stretch vibration in the FT-IR-RAS spectra before and after irradiation by a near-UV fluorescent lamp. The semilogarithmic plots of the photodegradation profiles of the various polymorphs were straight lines, including the induction period, indicating that degradation of the drug on the surface followed first-order kinetics. The induction periods of all forms were not significantly different. However, the degradation rate constant of form II at 12.0 Jcm^?2 s ^?1 was 5·1 and 1·5 times larger than those of forms I and III, respectively.     

The Use of Fourier Transform Infrared (FT-IR) Spectroscopy to Determine the Diffusion Coefficients of Alcohols in Polydimethylsiloxane

A variable long path gas cell was used to measure the sorption of organic vapors by a polymer slab. Unfilled polydimethylsiloxane (PDMS) slabs were cast and used to study the sorption of a series of aliphatic alcohols. The PDMS slab was suspended in the gas cell and exposed to low relative pressures of an alcohol vapor. The sorption rate of the alcohol vapor by the PDMS slab was obtained by measuring the decrease in the amount of free diffusant in the gas cell. The diffusion coefficients of the alcohols in the PDMS slab were then calculated from the curves of amount of diffusant sorbed versus time. The results show that the values of the diffusion coefficients at nearly infinite dilution, D ₀, for methanol, ethanol, 1-propanol, and 1-butanol are 1.01 × 10^–5, 0.61 × 10^–5, 0.54 × 10^–5, and 0.33 × 10^–5 cm²/sec, respectively. The isotherms for the sorption of the alcohols by the PDMS slab were also constructed from the data.     

Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes

Within the Process Analytical Technology (PAT) framework, it is of utmost importance to obtain critical process and formulation information during pharmaceutical processing. Process analyzers are the essential PAT tools for real-time process monitoring and control as they supply the data from which relevant process and product information and conclusions are to be extracted. Since the last decade, near infrared (NIR) and Raman spectroscopy have been increasingly used for real-time measurements of critical process and product attributes, as these techniques allow rapid and nondestructive measurements without sample preparations. Furthermore, both techniques provide chemical and physical information leading to increased process understanding. Probes coupled to the spectrometers by fiber optic cables can be implemented directly into the process streams allowing continuous in-process measurements. This paper aims at reviewing the use of Raman and NIR spectroscopy in the PAT setting, i.e., during processing, with special emphasis in pharmaceutics and dosage forms.     

美、英、欧三部药典近红外光谱分析方法概述

近红外光谱法(Near Infrared Spectropho tometry)是近年来受世界各国广为关注的一种药品分析方法。近红外光谱区波长范围为0.75～2.5μm,波数范围为13330～4000cm~(-1),分子在近红外区的吸收,主要是一些能量较低的电子跃迁,以及分子振动状态间的跃迁所产生的。由于频率较高,因此分子对其吸收主要是分子振动的信频吸收和合频吸收。 近红外光谱与红外光谱比较,不仅其谱带强度弱,而且波长短,因此不仅可检测不需任何物理、化