FTIR, XRD, and DSC analysis of the rosemary extract effect on polyethylene structure and biodegradability

The purpose of this research study was evaluation of the utility of two common multivariate techniques, agglomerative cluster analysis (CA) and principal component analysis (PCA), as supplementary means of detecting incompatibilities, which can occur between active pharmaceutical ingredients and excipients at the preformulation stage of a solid dosage form. For the detection of incompatibilities between atenolol (beta blocker) and selected excipients (mannitol, lactose, starch, methylcellulose, β-cyclodextrin, meglumine, chitosan, polyvinylpyrrolidone and magnesium stearate), the thermogravimetry (TG), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were chosen. The results have shown that compatibility between atenolol and an excipient can be identified in a CA dendrogram by two large clusters, from which one groups an excipient and physical mixtures with a high concentration of the excipient. Another cluster encompasses atenolol and mixtures with a high content of the drug. In the PCA plot, all samples are located along the first principal component axis (PC1), beginning from a single component located with the most negative PC1 value, through mixtures with gradually varying concentration of both ingredients, till the second component located close to the most positive PC1 values. The results have shown that CA and PCA fulfil their role as supporting techniques in the interpretation of the data acquired from the TG curves, and the obtained data are compatible with the results of DSC and FTIR analyses.     

Multivariate monitoring of soybean oil ethanolysis by FTIR

In this work, an analytical procedure was developed to monitor the ethanolysis of degummed soybean oil (DSO) using Fourier-transformed mid-infrared spectroscopy (FTIR) and methods of multivariate analysis such as principal component analysis (PCA) and partial least squares regression (PLS). The triglycerides (reagents) and ethyl esters (products) involved in ethanolysis were shown to have similar FTIR spectra. However, when the FTIR spectra derived from seven standard mixtures of triolein and ethyl oleate were treated by PCA at the region that represents the CO stretching vibration of ester groups (1700-1800 cm⁻¹), only two principal components (PC) were shown to capture 99.95% of the total spectral variance (92.37% for the former and 7.58% for the latter PC). This observation supported the development of a multivariate calibration model that was based on the PLS regression of the FTIR data. The prevision capability of this model was measured against 40 reaction aliquots whose ester content was previously determined by size exclusion chromatography. Only small discrepancies were observed when the two experimental data sets were treated by linear regression (R²=0.9837) and these deviations were attributed to the occurrence of non-modeled transient species in the reaction mixture (reaction intermediates), particularly at short reaction times. Therefore, the FTIR/PLS model was shown to be a fast and accurate method to predict reaction yields and to follow the in situ kinetics of soybean oil ethanolysis.     

Pattern recognition methods as supplementary techniques for identification of salicylamide — cyclodextrins inclusion complexes

The objective of this study was to learn whether or not the pattern recognition methods, such as agglomerative cluster analysis (CA) and principal component analysis (PCA), can be used as supplementary techniques for identification of salicylamide (SAA) inclusion complexes with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). To do this, phase-solubility of SAA in the presence of the cyclodextrins was studied by the Higuchi-Connors method, which showed that the cyclodextrins enhanced the solubility of SAA in water as compared to that of the drug. Next, the solid phase complexes of the drug with β-CD and HP-β-CD were prepared by using the coprecipitation, precipitation-evaporation, and kneading methods. Identification of the inclusion complexes was performed by using thermal analysis, infrared spectroscopy, and wide angle X-ray scattering. Two multivariate statistical methods, CA and PCA, were used as the supplementary techniques for identification of the inclusion complexes. The results of the statistical analysis have shown that CA and PCA are helpful for interpretation of the thermoanalytical and spectral data. Moreover, these methods enabled proper classification of the products in all doubtful cases. They can be used as supplementary techniques to verify the conclusions of the above-mentioned standard methods.      

Determination of antihypertensive mixtures by use of a chemometrics-assisted spectrophotometric method

A simple multivariate calibration method for analysis of two types of hypotensive mixture is described. The mixtures are composed of chlorthalidone with atenolol or chlorthalidone with both amiloride hydrochloride and atenolol. The components of the mixtures result in substantial spectral overlap—between 87.5 and 91.0%. Resolution of the mixtures under investigation has been accomplished mainly by using CLS and PCR methods. The components in each mixture have been simultaneously determined in three commercial dosage forms with high accuracy and without interference from commonly encountered excipients and additives. Good recoveries were obtained with both synthetic mixtures and commercial tablets. The results obtained were compared with those from pharmacopeial methods and found to be in good agreement. The results obtained from CLS and PCR were also compared with those obtained from a ¹D spectrophotometric method.     

Application of chemometrically processed thermogravimetric data for identification of baclofen-excipient interactions

Studies are constantly being conducted on the elaboration of efficient methods to confirm the compatibility of active pharmaceutical ingredients (APIs) and excipients, since medicinal products, apart from their APIs, also contain numerous excipients that not only have important functions in pharmaceutical preparations but can also initiate or participate in interactions with drug substances, which eventually lead to a decline in drug quality. With this in mind, research was undertaken to evaluate two of the most often applied pattern recognition methods, hierarchical cluster analysis (HCA) and principal component analysis (PCA), as supporting techniques in the identification of potential physicochemical interactions that may occur during the preformulation of solid dosage forms. The investigation performed with the use of baclofen and selected excipients has shown that with thermogravimetric analysis, HCA and PCA fulfill their role as supporting techniques in the interpretation of the data obtained. Based on these methods, it is possible to detect incompatibilities between baclofen and excipients, and the data obtained concur strongly with the results of differential scanning calorimetry and IR spectrometry analyses.     

6-Hydroxymethyltriazolyl-6-deoxy-β-cyclodextrin: a highly water soluble and structurally well-defined β-cyclodextrin click cluster

The structural, physical, and biological properties of heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HTβCD) were investigated by a variety of methods, including NMR, UV/vis, circular dichroism spectroscopy, computer modeling, turbidity testing, K_a measurements, and the MTT assay. The experimental results suggest that HTβCD is structurally well-defined, highly water-soluble, and has low cytotoxicity. These advantages of HTβCD versus β-CD indicate that β-cyclodextrin click clusters may function both as host molecules and as potential, alternative excipients to β-CD.     

Investigation of inclusion complexes of citronella oil, citronellal and citronellol with β-cyclodextrin for mosquito repellent

The aim of this study was to prepare the inclusion complexes of citronella oil, citronellal or citronellol with β-cyclodextrin and evaluate their physicochemical properties using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). A kneading method was employed to prepare the inclusion complexes and weight ratios of each of the active substance to β-cyclodextrin were 1:1 (1:1 CPX) and 1:2 (1:2 CPX). For comparison purposes, physical mixtures of these active compounds and β-cyclodextrin were also prepared and investigated. Unlike the physical mixtures, the SEM technique revealed drastic changes in the shapes and morphologies of the particles for the inclusion complexes. Furthermore, the FTIR and DSC results seemed to reveal some interactions between the active substance and β-cyclodextrin. The o/w lotions, which contained 10% w/w citronella oil (normal citronella oil; 1:1 CPX or 1:2 CPX), were formulated using Cremophors as emulsifiers. With modified Franz diffusion cell and synthetic membrane, the release rates of citronella oil from the lotions containing the inclusion complexes were significantly lower than that from the prepared lotion containing normal citronella oil. The mosquito (Aedes aegypti) repellent efficacy of the lotions containing citronella oil, citronellal or citronellol (both normal and inclusion complexes) was further evaluated by human-bait technique. The highest mosquito repellent activity was observed in the formulation which contained citronella oil–β-cyclodextrin inclusion complex at weight ratio of 1:1.     

Physico-Chemical Stability of Warfarin in Ground Mixtures with β-Cyclodextrin or Microcrystalline Cellulose under Storage Conditions

The effects of grinding and the excipients used on the solid state stability of warfarin in ground mixtures with β-cyclodextrin or microcrystalline cellulose have been investigated by using x-ray powder diffractometry, IR spectrophotometry and differential scanning calorimetry. The grinding process did not result in warfarin-excipient interaction, but caused a crystalline form of warfarin to transfer to an amorphous state in the presence of β-cyclodextrin. The stability of this amorphous state of warfarin in tablets made from the ground mixtures stored at 37°C and 75% RH (relative humidity) was also studied. There was only a small amount of amorphous warfarin in tablets that recrystallized under storage conditions. The recrystallization of amorphous warfarin might be due to moisture adsorption. β-cyclodextrin possesses an ability to prevent the recrystallization of large amounts of amorphous warfarin in tablets stored at 37°C and 75% RH.     

Drug-excipient compatibility studies by physico-chemical techniques; The case of Atenolol

We apply a range of techniques (thermal methods, microscopy, X-ray diffraction, IR spectroscopy) to characterize a drug (atenolol), several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©) and drug-excipients mixtures either as prepared, annealed, and exposed to moisture. We compare the data of the mixtures with those computed from a weighted average of similarly treated pure compounds to find evidence of drug properties modified by the interaction with the excipient. We find that thermal response is by far the most sensitive indicator of interaction while IR is the least sensitive one. Avicel© has essentially no interaction with atenolol, while MGST modifies significantly only the thermal response of the drug in the MGST-rich mixtures. PVP interacts strongly with atenolol, and this interaction appears to be mediated by the substantial amount of hydration water the excipient brings in its mixtures with a water-free drug.     

Comparison and improvement of commonly applied statistical approaches for identification of plant species from IR spectra

Fourier transform infrared spectroscopy (FTIR) has been studied many times in the context of identification of plant, fungal and bacterial species. Infrared spectra are commonly analyzed using multivariate statistical methods such as cluster analysis (CA), principal component analysis (PCA), partial least squares analysis (PLS) and discriminant analysis (DA). In this study, a univariate statistical method for analysis of variance (ANOVA) was used to reduce the number of variables before applying the multivariate methods. Analyzing variables using ANOVA or a combination of ANOVA with CA produced better results. Here, experiments were carried out by performing ANOVA using the first derivative of the spectra instead of the original spectra or its second derivative because using the first‐derivative variables led to improved distinction between species. Different results were obtained by applying different validation methods. The leave‐one‐out validation method gave higher results than the validation‐with‐training and validation sample sets, thus indicating the non‐objectivity of the leave‐one‐out validation method. Copyright © 2010 John Wiley & Sons, Ltd.     

DSC,FT-IR and NIR with Chemometric Assessment Using PCA and HCA for Estimation of the Chemical Stability of Oral Antidiabetic Drug Linagliptin in the Presence of Pharmaceutical Excipients

Pharmaceutical excipients should not interact with active substances, however, in practice, they sometimes do it, affecting the efficacy, stability and safety of drugs. Thus, interactions between active substances and excipients are not desirable. For this reason, two component mixtures of oral antidiabetic drug linagliptin (LINA) with four excipients of different reactivity, i.e., lactose (LAC), mannitol (MAN), magnesium stearate (MGS) and polyvinylpyrrolidone (PVP), were prepared in a solid state. A high temperature and a high humidity of 60 °C and 70% RH, respectively, were applied as stressors in order to accelerate the potential interactions between LINA and excipients. Differential scanning calorimetry (DSC) as well as Fourier transform infrared (FT-IR) and near infrared (NIR) spectroscopy were used to estimate the changes due to potential interactions. In addition, chemometric computation of the data with principal component analysis (PCA) and hierarchical cluster analysis (HCA) was applied to adequately interpret the findings. Of the excipients used in the present experiment, all of them were not inert in relation to LINA. Some of the interactions were shown without any stressing, whereas others were observed under high-temperature/high-humidity conditions. Thus, it could be concluded that selection of appropriate excipients for LINA is very important question to minimize its degradation, especially when new types of formulations with LINA are being developed and manufactured.     

Towards the identification of plant and animal binders on Australian stone knives

There is limited information regarding the nature of plant and animal residues used as adhesives, fixatives and pigments found on Australian Aboriginal artefacts. This paper reports the use of FTIR in combination with the chemometric tools principal component analysis (PCA) and hierarchical clustering (HC) for the analysis and identification of Australian plant and animal fixatives on Australian stone artefacts. Ten different plant and animal residues were able to be discriminated from each other at a species level by combining FTIR spectroscopy with the chemometric data analysis methods, principal component analysis (PCA) and hierarchical clustering (HC). Application of this method to residues from three broken stone knives from the collections of the South Australian Museum indicated that two of the handles of knives were likely to have contained beeswax as the fixative whilst Spinifex resin was the probable binder on the third.     

Synthesis,characterization of inclusion compounds of amygdalin with β-cyclodextrin and sod-like activity and cytotoxicity on hela tumor cells

In this work is presented the synthesis of the inclusion complexes of amygdalin with β-cyclodextrin by three methods: kneading, co-precipitation and freeze drying and their characterization.The inclusion compounds were synthesized using a molar ratio of amygdalin: β-cyclodextrin of 1:1. Synthesized compounds were analyzed by FTIR spectroscopy, X-rays, thermal analysis and the results confirm the formation of inclusion compounds by amygdalin with β-cyclodextrin.The studies carried out have shown the protective effect of amygdalin-β-cyclodextrin compounds obtained by freeze drying, kneading and coprecipitation against free radicals (SOD-like activity in vivo) and the results of in vitro cell cytotoxicity of the compounds on HeLa cell line compared to pure amygdalin. Compound obtained by freeze drying has the best SOD-like activity and cytotoxicity on HeLa tumor cells, so it may be considered as potential therapeutic agent.     

交叉响应传感器鉴别β受体激动剂及其混合体系

开发了一种鉴别β受体激动剂的新型阵列传感器。该传感器由8种传感物质构成,使用96孔板酶标仪采集响应数据,结合主成分分析(PCA)、分层聚类分析(HCA)、判别分析(LDA)等模式识别方法进行数据处理,对5类β受体激动剂及其混合物进行检测。PCA结果表明,该传感器主要是基于空间结构以及氢键作用实现对β受体激动剂的识别;HCA结果显示,93个分析样本归类正确;LDA结果显示,该传感器对于β受体激动剂识别的准确率达98.9%。本方法在β受体激动剂的检测中有潜在应用价值。     

Comparative study between three methods of outlying detection on experimental results

This paper describes experimental results through multivariate statistical methods that might reveal outliers that are rarely taken into account by analysts. The results were submitted to three procedures to detect outliers: Mahalanobis distance, MD, cluster analysis, CA, and principal component analysis, PCA. The results showed that although CA is one of the procedures most often used to identify outliers, it can fail by not showing the samples that are easily identified as outliers by other methods, like MD. Mahalanobis distance proved to be the simpler application, with sensitive procedures to identify outliers in multivariate datasets.     

Synthesis and characterization of a poly[2,7-(9,9-dioctylfluorene-alt-2,7-fluorene/β-CD)] main chain polyrotaxane

Poly[2,7-(9,9-dioctylfluorene-alt-2,7-fluorene/β-CD)] main chain polyrotaxane was synthesized through organometallic Suzuki coupling by reacting β-cyclodextrin/2,7-dibromofluorene inclusion complex with 9,9-dioctylfluorene-2,7-bis(trimethyleneborate). The IR, NMR and elemental analysis data support the presence of β-cyclodextrin in the copolymer structure. No glass transition or melting phenomena were detected in DSC curves of the polyrotaxane on the heating run in the 50-250 ° range. As compared with the reference copolymer obtained in the absence of β-cyclodextrin, the rotaxane copolymer is more hygroscopic and soluble in polar/non-polar solvent mixtures. The expected modification of the optical properties of the fluorene copolymer with rotaxane architecture in the main chain was proved by fluorescence and UV-vis spectroscopy and consists in a blue-shifted emission.     

Physicochemical characterization of coumestrol/β-cyclodextrins inclusion complexes by UV–vis and FTIR-ATR spectroscopies

The inlcusion behaviour of unsubstituted β-cyclodextrin (β-CyD) and (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD), in solution and solid state was studied with regards to a poorly water-soluble bioflavonoid, coumestrol (Coum), namely 7,12-dihydroxycoumestan, well-known for its anti-oxidant, anti-inflammatory, anti-fungal and anti-viral activities. Phase-solubility measurements were performed to evaluate in solution the complexation of the two cyclodextrins, i.e. β-CyD and HP-β-CyD. The stoichiometry and stability constants of the Coum/β-CyD and Coum/HP-β-CyD complexes were calculated by the phase-solubility method, after which drug–cyclodextrin solid systems were prepared by co-precipitation. In solid phase, the formation of inclusion complexes was confirmed by Fourier transform infrared spectroscopy in attenuated total reflectance (FTIR-ATR) geometry. In particular, complexation mechanisms were explained by the significant differences revealed in the FTIR-ATR spectra of physical mixtures with respect to those of the complexes; the use of deconvolution and curve fitting was determinant.     

Micro spectroscopy FTIR reflectance examination of paint binders on ground chalk

Summary A restorer's questions on chemical analysis of paint binders to support his complicated work has always had an exceptional appeal for chemists. Non-destructive surface analysis of rather complex materials such as paint binders is possible. The advantages of vibrational spectroscopy related to the details about chemical structure of organic compounds have been combined with sophisticated methods of multivariate data analysis. Reflectance spectra of several paint binders on ground chalk were measured using a fast, sensitive FTIR spectrometer equipped with an infrared microscope. The initial reflectance spectra include sufficient structural information to allow successful classification by hierarchical cluster analysis (HCA). Similarities between the several binders are plotted as dendrograms which are well structured. Their explanation will be discussed in detail. Finally the postulated feature sets will be checked up by principal component analysis (PCA) as to their relevance and information content.     

On the use of dispersed nanoparticles modified with single layer beta-cyclodextrin as chiral selecor to enhance enantioseparation of clenbuterol with capillary electrophoresis

A new strategy for chiral separation by capillary electrophoresis employing modified-nanoparticles as chiral selector is described for clenbuterol analysis. Nanoparticles modified with β-cyclodextrin (β-CD) form a large surface area platform to serve as a pseudostationary chiral phase, which can be applied for the enhancement of the enantioseparation. The application of four kinds of nanoparticles was investigated (multi-walled nanotubes (MWNTs), polystyrene (PS), TiO₂ and Al₂O₃) modified with single layer β-CD as chiral selector in the enantioseparation of clenbuterol by capillary electrophoresis (CE). Successful clenbuterol enantioseparation could be achieved with the β-CD-modified MWNTs as chiral selector. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) confirmed the β-CD modification of the nanoparticles. The effects of nanoparticles, surfactant, chiral selector (β-CD) and run buffer were studied in relation to the enantiomeric separation of clenbuterol. This study opens attractive perspectives for the use of modified nanoparticles for chiral separational purposes in CE.