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Applied Spectroscopy Reviews
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Application of Fourier Transform Infrared Spectrophotometry in Pharmaceutical Drugs Analysis
Andrei A. Bunaciua; Hassan Y. Aboul-Eneinbc; Serban Fleschind a CROMATEC_PLUS SRL, Analytical Research Department, Bucharest, Romania b Pharmaceutical and Medicinal Chemistry Department, Pharmaceutical and Drug Industries Research Division, Dokki, Cairo, Egypt c Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia d Department of Organic Chemistry, Faculty of Chemistry, University of Bucharest, Panduri, Bucharest, Romania Accepted uncorrected manuscript posted online: 09 February 2010 Online publication date: 09 February 2010 To cite this Article Bunaciu, Andrei A. , Aboul-Enein, Hassan Y. and Fleschin, Serban(2010) 'Application of Fourier
Transform Infrared Spectrophotometry in Pharmaceutical Drugs Analysis', Applied Spectroscopy Reviews, 45: 3, 206 — 219, doi: 10.1080/00387011003601044, First posted on: 09 February 2010 (iFirst) To link to this Article: DOI: 10.1080/00387011003601044 URL: http://dx.doi.org/10.1080/00387011003601044
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it is suitable for analysis of solid. Indeed. As a consequence of improved instrumentation.2. Cairo. Egypt.1080/00387011003601044 Application of Fourier Transform Infrared Spectrophotometry in Pharmaceutical Drugs Analysis ANDREI A. It is not meant to be complete or exhaustive but to provide the reader with sufﬁcient background for selected applications in pharmaceutical analysis. it can become a powerful tool for the pharmaceutical industry. 2). in production for process monitoring. College of Pharmacy. and biotechnological pharmaceutical forms.3 AND SERBAN FLESCHIN4 1 Downloaded By: [UNICAMP] At: 23:19 1 June 2010 CROMATEC PLUS SRL. LLC ISSN: 0570-4928 print / 1520-569X online DOI: 10. Riyadh. Dokki.000 nm. Analytical Research Department. This review focuses on pharmaceutical FTIR applications used for qualitative and quantitative analysis. Saudi Arabia 4 Department of Organic Chemistry. Cairo 12311. Egypt 3 Department of Pharmaceutical Chemistry. E-mail: enein@gawab. Romania 2 Pharmaceutical and Medicinal Chemistry Department. 2010 Copyright © Taylor & Francis Group. Moreover. The classical infrared region extends from 2. Bucharest. drug analysis. University of Bucharest.500 to 50. Faculty of Chemistry. This spectral region encompasses three Address correspondence to Professor Hassan Y. Aboul-Enein. 45:206–219. quality control INTRODUCTION Infrared (IR) spectroscopy is one of the most important analytical techniques available to scientists. Pharmaceutical and Drug Industries Research Division. liquid. Romania Abstract: This review provides some background to infrared spectroscopy including Fourier transform infrared spectroscopy.com 206 . King Saud University. ABOUL-ENEIN. Pharmaceutical and Medicinal Chemistry Department. Bucharest. Panduri. The infrared region starts immediately after the visible region at 700 nm. Keywords: FTIR analysis. it can be implemented during pharmaceutical development. and in quality control laboratories. One of the great advantages of IR spectroscopy is that any sample in virtually any state may be studied. BUNACIU. a variety of new sensitive techniques have now been developed in order to examine formerly intractable or difﬁcult samples (1. Dokki.Applied Spectroscopy Reviews.1 HASSAN Y. Associated with chemometrics. Pharmaceutical and Drug Industries Research Division. Fourier transform infrared spectroscopy (FTIR) is a fast and nondestructive analytical method.
Besides. IR spectroscopy is based on the absorption of electromagnetic radiation by a molecular system.76– 2. the entire IR spectra of an organic compound provide a unique ﬁngerprint. and can thus be used for quantitative purposes. mid-infrared (MIR: 4. characteristic absorption bands can be used for compound-speciﬁc detection. and intra. Finally.000–400 cm−1 or 2.000 cm−1 or 0. The IR spectrum of a poly-atomic molecule is based on molecular vibrations. IR spectroscopy is nondestructive and allows in situ and remote measurements of almost any sample. The reader interested in details of the basic principles of vibrational spectroscopy and the interpretation of vibrational spectra is referred to relevant books (4–7). due to the great advantages it provides (10–14). and their immediate environment. (1): [cm−1 ] = 1 [nm] × 10−7 (1) The basic principle of IR spectroscopy is the measurement of the amount of IR radiation.and intermolecular interactions. Moreover. Fourier transform [FT]) or to avoid too large numbers in the NIR range where nm is more often used. named in relation to the visible region. As a consequence. The energies of infrared radiation range from 48 kJ mol−1 at 2. Infrared spectroscopy is often called vibrational spectroscopy.000 µm).FTIR in Pharmaceutical Drugs Analysis 207 subdivisions: the far-infrared (FIR: 400–10 cm−1 or 26–1. liquid. their conformation. At this point it is important Downloaded By: [UNICAMP] At: 23:19 1 June 2010 . The ﬁrst one is the most popular.000–4. FTIR spectrometry is a fast analytical technique that provides very interesting qualitative and quantitative information from solid. 9). IR spectra provide images of vibrations of the atoms of a compound. These characteristic bands form the empirical basis for the interpretation of vibrational spectra. and near-infrared (NIR: 13. The choice of one of the units depends either on the type of spectrometer (dispersive vs. Two units are used in vibrational spectroscopy: cm−1 (wavenumbers) or nm. most compounds can be unambiguously identiﬁed on the basis of their IR spectra.000 nm. which is absorbed (or emitted) by a sample as a function of the wavelength (3). when reference spectra are available. and gaseous samples.6 µm).500 nm to 2. In other words. Infrared spectroscopists often use wavenumbers to describe the infrared spectral region. The position and intensity of a vibrational band are characteristic of the underlying molecular motion and consequently of the atoms participating in the chemical bond. The IR measurement can be carried out in the modality of transmission or reﬂectance. The vast majority of molecules exhibit infrared bands in the mid-infrared region between 400 and 4. An IR spectrum is obtained by passing infrared radiation through a sample and determining what fraction of the incident radiation is absorbed at a particular frequency.000 cm−1. The introduction of Fourier transform infrared (FTIR) instrumentation generated a true revolution in IR spectrometry. Thus. The major advantage of IR over other spectroscopic techniques is that practically all compounds show absorption (emission) and can thus be analyzed both qualitatively and quantitatively. The relationship between the two units is given by Eq. IR spectroscopy has a high potential for the elucidation of molecular structures. irrespective of the physical state and without elaborate sample preparation (8.6–26 µm). similar to that described by Beer-Lambert’s law.4 kJ mol−1 at 50. a certain submolecular group produces bands in a characteristic spectral region. Therefore. which can be readily distinguished from the IR absorption pattern of other compounds including isomers. These low energies are not sufﬁcient to cause electron transitions but they are sufﬁcient to cause vibrational changes within molecules. bond strengths. IR spectroscopy obeys a law. each speciﬁcally dependent on atomic masses.
The application of this technique has improved the acquisition of IR spectra dramatically. the interferogram. the beam splitter. quality control. The heart of the optical hardware in such FT spectrometers is the interferometer. The classic two-beam Michelson interferometer is shown schematically in Figure 1 and consists of two mutually perpendicular plane mirrors: a ﬁxed mirror and a movable one. The signal actually registered by the detector. Prior to a review on this subject. leaves the interferometer and is ﬁnally focused on the detector as shown in Figure 2. In the major section quantitative and qualitative determination of active principle ingredient (API) content in different dosage forms will be presented in alphabetic order of the API. Bunaciu et al. covering the period between 2005 and 2009. A beam emitted by a source is split in two by the beam splitter. and hits the beam splitter again. Because the two split beams are spatially coherent. they interfere on recombination. bisects the planes of these two mirrors.208 A. The beam. Schematic of a Michelson interferometer. to point out that the use of IR for quantitative purposes has grown dramatically in recent years. is thus Figure 1. A. The same happens to the transmitted radiation. . The reﬂected part of the beam travels to the ﬁxed mirror. and manufacturing process supervision of pharmaceutical drugs. FTIR was originally a spectroscopic technique to identify the functional groups of chemical constituents but has been widely used and applied in recent years for the identiﬁcation. The objective of this article is to review new developments in applications of FTIR spectroscopy in pharmaceutical or drug analysis. modulated by the movement of the mirror. FOURIER TRANSFORM INFRARED TECHNIQUE Downloaded By: [UNICAMP] At: 23:19 1 June 2010 FTIR spectrometers have almost entirely replaced dispersive instruments because of their improved performance in nearly all respects. A semi-reﬂecting mirror. is reﬂected there. it is useful to give a short introduction to the concept of the FTIR technique and to brieﬂy explain the principles of attenuated total reﬂection (ATR) as well as diffuse reﬂectance infrared spectroscopy (DRIFTS) methods.
Moreover. In most cases. In the case of FTIR spectroscopy. Transmission analysis requires the sample to be partly transparent. Liquid can be prepared as a dilute solution in a cell. Schematic of an FTIR spectrometer. samples must be diluted in nonabsorbing matrix.FTIR in Pharmaceutical Drugs Analysis 209 Figure 2. The mathematics of the conversion of an interferogram into a spectrum is the Fourier transformation. . The ratio of the former to the latter is the IR transmission spectrum of the sample. the powder particle size must be smaller than the radiation wavelength to avoid the Christiansen scattering effect. It is not possible with thick samples such as tablets. Based on fully developed software. a computer performs this transformation. Solid samples are dispersed usually in a potassium bromide (KBr) disk or mull. the sample is usually placed between the interferometer and the detector. no light might be transmitted to the detector. otherwise. in the MIR range. Transmission has been extensively used to analyze thin samples such as ﬁlms (15) or tissues (16). the source illuminates the sample and the detector is placed behind the sample (Figure 3) to acquire the fraction of light transmitted through the sample. In transmission measurement. Source Sample Detector Figure 3. Downloaded By: [UNICAMP] At: 23:19 1 June 2010 the radiation intensity of the combined beams as a function of the position of the movable mirror. The essential steps for obtaining an FTIR spectrum are to produce an interferogram with and without a sample in the beam and then to transform these interferograms into spectra of the source with sample absorption and the source without sample absorption. which appears as band distortion in the spectra (4). Schematic representation of transmission measurements.
is given (17) by Eq.g. (2): dp = λi 2π n1 sin2 θ − n2 21 1/2 (2) where λ is the wavelength. The use of ATR in spectroscopy is based upon the fact that although completed internal reﬂection occurs at the sample–crystal interface. Unfortunately. the crystal will degrade with surface scratching and cracking. A. or germanium [Ge]). usually made of zinc selenide [ZnSe]. Bunaciu et al.210 A. In attenuated total reﬂection. and then directed to the detector by another set of mirrors. The IR beam from the spectrometer is focused onto the beveled edge of the ATR element by a set of mirrors. Furthermore. but an intimate optical contact between the sample and the ATR crystal is crucial. dp . Figure 4.. Downloaded By: [UNICAMP] At: 23:19 1 June 2010 In reﬂection measurement. Schematic representation of ATR crystal. n1 and n2 are the refractive indices of the ATR crystal and the sample. Eq. respectively. The penetration depth. the sample is placed in optical contact against a special crystal. Figure 5. Schematic representation of DRIFTS measurements. the penetration depth of the beam depends on the wavelength. The sample is presumed inﬁnitely thick and incapable of transmission. reﬂected through the crystal. the detector is placed on the same side of the sample as the source to record the signal reﬂected by the sample. which is composed of a material with a high index of refraction (e. Samples examined by FTIR-ATR generally require minimal or no sample preparation. diamond. and θ is the angle of incidence. silicon [Si]. (1) shows that total reﬂection occurs when the angle of incidence is larger than the critical angle θ = sin−1(n2 /n1 ). Obviously. . termed the ATR crystal. radiation does in fact penetrate a short distance into the sample (see Figure 4). The two types of reﬂection measurement commonly used in CI analysis of pharmaceutical forms are attenuated total reﬂection (ATR) and diffuse reﬂection (DRIFTS).
X-ray diffractometry (XRD). In the MIR range.500–750 cm−1) was Downloaded By: [UNICAMP] At: 23:19 1 June 2010 .700 cm−1 corresponding to crystal water. Bucillamine. The FTIR spectral patterns of the anhydrous and hydrate forms of nitrofurantoin also exhibited signiﬁcant differences. tablets.0%).. A Fourier transform infrared spectrometric method was developed for the rapid.g. were used in data processing. Conventional KBr spectra were compared for the best determination of the active substance in drug preparations. Of all the analytical tools applied. A fraction of this light is reﬂected by the sample and recorded by the detector (Figure 5). representing 20% of all mammalian species. partial least squares (PLS) and principal components regression (PCR+) methods. incoming radiation interacts with the sample and is scattered by interaction with the particles. direct measurement of ascorbic acid (vitamin C) and biotin (vitamin H) in different pharmaceutical products. and the authors suggest the use of the PCR+ method because of the smaller value of relative standard devaiaition (RSD. FTIR spectrometry was used for the rapid. even though pharmacopoeia had introduced (omologated) FTIR spectroscopy for such determinations. SELECTED PHARMACEUTICAL APPLICATIONS The literature studied shows a great number of papers dedicated to pharmaceutical drug analysis using FTIR. N-(2-mercapto-2-methylpropionyl)-lcysteine. because samples need no dilution at all in the NIR range (the bands are weak). The Beer-Lambert law and chemometric approaches were applied in data processing (23).605. were characterized by powder DRIFTS.500–3. only DRIFTS was able to indicate the formation of hydrogen bonds between the molecules of the anhydrous drug substance and crystalline water uptaken from atmospheric moisture as evidenced by the signiﬁcant absorption at 3. but there are also many papers dedicated to quantitative methods. and a small number of other species such as the guinea pig and a few species of birds and ﬁsh. e. <3. Vitamin H or B7 is a water-soluble B-complex vitamin composed of a ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. Signiﬁcant differences were observed in the DRIFTS patterns between the anhydrous and hydrate forms of ampicilline. Beer-Lambert’s law and two chemometric approaches. Most of the papers are related to qualitative assay of an active compound.FTIR in Pharmaceutical Drugs Analysis 211 In diffuse reﬂection. direct measurement of bucillamine (25). The authors studied the possibility of using the Beer-Lambert law for the quantitative determination of ASA in pharmaceutical products at 1. MIR-DRIFTS is rarely used for imaging. For this reason. in both anhydrous and hydrate forms. Ampicilline and nitrofurantoin. A good similarity between the spectra in the ﬁngerprint region (1. A Fourier transform infrared spectrometric method was developed for the rapid and direct measurement of acetylsalicylic acid (ASA) in different pharmaceutical products (22). its use has not been reported in the literature. and thermogravimetric and differential thermal analyses (TG/DTA) (21).49 cm−1. DRIFTS. nontransparent samples in various noninvasive applications such as pharmaceutics (19. The results are very similar. NIR-DRIFTS is widely used for the image analysis of thick. is a novel disease-modifying antirheumatic drug. 20). Vitamin C is an essential nutrient for a large number of higher primate species (24). On the other hand. Conventional KBr spectra were compared for the best determination of active substances in drug preparations. DRIFTS requires the sample to be diluted between 10 and 100 times to avoid saturation and band distortion (18). Conventional KBr-spectra and DRIFTS spectra were compared for best determination of active substance in drug preparations.
III. A. Diffuse reﬂectance FTIR spectroscopy coupled with modern multivariate calibration methods.125 to 1.0%). Similar results were obtained with both chemometric methods. direct measurement of chromium (tris) picolinate [Cr(pic)3 ] in different pharmaceutical products.600 cm−1) were selected and the data were partitioned into training and test subsets applying the Kennard-Stone design. PLS and PCR+ methods.000 and 400 cm−1 and the second range was 2. by using DRIFTS spectral data subjected to the standard normal variate transformation (row centering and scaling) and to the lazy learning algorithm (26). Calibration models were generated by PLS method over the wavelength ranges of 450–1. In both cases no blanks were ﬁrst selected. but after calibration was performed. were used in data processing (28).515–3.000– 400 cm−1. It was found that all the selected algorithms perform better than the PLS regression (root mean squared error of prediction [RMSEP]) from 3. but the authors suggest the use of the PCR+ method because of the smaller value of RSD (<2. were subjected to the blank function. A fast and simple nondestructive method was developed for quantiﬁcation of form IV in form III. support vector machines (SVMs). namely. with the exclusion of the spectral regions from 1. to which a blank function has been applied. (25) (DRIFTS and KBr-disk). and a form (C-monoclinic or form IV) less soluble than the pharmaceutically acceptable (P-monoclinic or form III) can be formed under various conditions during drug formulation. composed of cyclosporine samples characterized by different percentages of amorphous cyclosporine.212 A. quantitative analysis of form IV in form III is important to the drug formulators. The mixing of different percentages of crystalline cyclosporine with amorphous cyclosporine was used to obtain a set of standards. PLS and PCR+ methods. The results obtained using chemometric approaches are much higher than the expected values.200 cm−1. Beer-Lambert’s law and the two chemometric approaches. The results are very similar.2%). A study in the development of a quantiﬁcation method to detect the amount of amorphous cyclosporine (cyclosporine A) using FTIR was performed (30). with known bioavailability problems related to its polymorphism. The ﬁrst range used was between 4. Bunaciu et al. and partial least squares (PLS) regression. Two spectral regions (675–1.515 cm−1 and from 3. The regions where crystalline and amorphous cyclosporine spectra are essentially similar. taking into account that the determination was made possible using Beer-Lambert’s law.200 to 4. the computer itself selects ranges of blanks due to the thresholds. and IV) (27). and the authors suggest the use of the method that demands a blank with the principal excipient because of the smaller value of RSD (about 2. Carbamazepine is a poorly soluble drug.125 cm−1 and 1. in this study for the quantiﬁcation of carbamazepine crystal forms in ternary powder mixtures (I. artiﬁcial neural networks (ANNs) in two versions (ANNraw and ANN-pca). Conventional KBr spectra were compared for best determination of active substance in drug preparations. were used in data processing (29). direct measurement of coenzyme Q10 (CoQ10) in different pharmaceutical products.0%).180 and 3. An FTIR spectrometric method was developed for the rapid. and consequently are not indicative of signiﬁcative differences between the two forms. Beer-Lambert’s law and two chemometric approaches. The data interval was expanded and parts of the spectra were eliminated to reduce the size of the data matrix required by the calibration modeling. Conventional KBr spectra were compared for the best determination of active substance in drug preparations.0 to 8. lazy learning (LL). Two chemometric approaches.000 cm−1. Downloaded By: [UNICAMP] At: 23:19 1 June 2010 . PLS and PCR+ methods.400– 3. A spectrometric method was developed for the rapid. were used in data processing. obtained using the two methods proposed by Bunaciu et al. Therefore.
FTIR in Pharmaceutical Drugs Analysis 213 Diclofenac sodium (DS) is a nonsteroidal antiinﬂammatory drug widely used in painful and inﬂammatory diseases. FTIR spectroscopy was a useful tool to distinguish the new form from DS and DSH: DSH3 exhibited signiﬁcant differences in the observed vibrational transitions in the 3. were used in data processing. Iran) (35).488–1. These spectral data were converted to −log(R/R0 ) and Kubelka–Munk units. There are a number of situations when there is a need to determine the concentrations of components in solid-state mixtures without dissolving the sample. The peaks in the DHEA-MCC spectra are a little more evident than in the DHEA-KBr one. and subjected to PLS analysis.315 cm−1 and 1.000 cm−1 range of frequencies. Tehran. Diffuse reﬂectance infrared Fourier transform spectroscopy coupled with PLS data analysis has been used to determine the minor component in a mixture of structurally similar solid-state compounds. and thermal analysis were used for the identiﬁcation and the characterization of DSH. Data from FTIR spectroscopy. The differences in the IR spectra of ephedrine and pseudoephedrine are due to differences in the intermolecular interactions between the molecules in the solid-state forms. direct measurement of dehydroepiandrosterone (DHEA) in drugs (33). Conventional KBr spectra and KBr + 2. A novel analytical procedure has been developed for quantitative determination of levodopa and carbidopa in aqueous binary solutions acidiﬁed by HCl and without any other sample pretreatment. X-ray patterns. XRD.000 cm−1).800 cm−1 wavenumber range (36). The main aim is to ﬁnd wavelengths that produce signiﬁcant improvements in PLS prediction. and thermal analysis were used for identiﬁcation and characterization of DSH3 in comparison with the anhydrous form (DS. It is of interest to mention that there are no signiﬁcant changes between the two spectra in the ﬁngerprint region (under 2. a tetrahydrate form different from that obtained by crystallization from water and previously described. the anhydrous form DS gives rise to a hydrate species DSH. rapid. There is. The method is based partially on least squares treatment of data obtained by ATR-FTIR spectrometry in 1. An FTIR spectrometric method was developed for the rapid. and convenient analytical method without sample handling procedures is proposed for the determination of niﬂumic acid in a pharmaceutical gel with ATR/FTIR Downloaded By: [UNICAMP] At: 23:19 1 June 2010 . PLS and PCR+ methods. Two chemometric approaches. they have properties similar to that of polymorphs. assembled into data ﬁles. The authors suggest the use of the PCR+ method because the peak to peak error value must be a maximum of ﬁve times greater than the RMS error value. hence.550 cm−1 spectral regions. The simple. A new method is presented for quantitative determination of naltrexone in aqueous solutions based up on the wavelength selection in mid-FTIR spectra using PLS technique. Plus the concentration values of DHEA/tablet are a little higher in DHEA-MCC than in DHEA-KBr because of possible interfering signals in spectra. in this case mixtures of ephedrine and pseudoephedrine (34). for example. Data from FTIR spectroscopy. rapid. and thermal behavior (31).211–1. A simple. XRD. a difference in the frequency of the O-H stretching vibration in the two forms. the commercial form) and the hydrate form DSH (obtained by exposure of DS to relative humidity even below 60%).600–2.0 mg MCC (microcrystalline cellulose) spectra were compared for best determination of the active substance in drug preparations. The best results were obtained with PCR+ method. by exposure to relative humidity even below 60% at 25◦ C. In standard conditions. and accurate proposed method was applied to determine levodopa and carbidopa in Levodopa-C R tablets (Alborz Daruou Pharmaceutical Company. The methods of preparation of the trihydrate form (named DSH3) were described and its physicochemical properties were investigated (32). PLS wavelength selection treatment is performed on the data obtained by ATR-FTIR spectrometry in 830–1. DS and DSH were easily differentiated by their FTIR spectra.
During the aging process. All spectra were obtained in the transmittance mode. Chemical images of compacted pharmaceutical tablets were obtained in situ using a miniature compaction cell and a diamond ATR accessory (43). An analytical reﬂectometric method that has an objective not only of industrial quality control but detecting possible falsiﬁcations and/or adulterations of propranolol in pharmaceutical formulations was proposed (39). respectively. The IR spectroscopy gives conﬁdence of 98. such as simplicity and extremely low consumption of reagents. The used spectral range of niﬂumic acid for the establishment of this model was 2.616 cm−1 (attributed to Phen and Salo.300– 1. and a broadening of the carbonyl band (41). such modiﬁcations included a decrease of unsaturation index.100 cm−1. Bunaciu et al. microcrystalline cellulose. lactose. which were collected at axially cut surfaces of the ﬂat-faced matrix tablets.6-dichloroquinone-4-chloroimide (II) using ﬁlter paper as solid support. FTIR spectroscopy can be interesting in stability studying of cosmetic or pharmaceutical oil-in-water (O/W) emulsions. and lactose. Model excipients and drug used in these experiments were avicel. A PLS procedure in combination with infrared spectroscopy has been developed for simultaneous determination of sulphamethoxazole (SMZ) and trimethoprim (TMP) in raw material powder mixtures used for manufacturing commercial pharmaceutical products (39). The method is based on the diffuse reﬂectance measurements of the colored product (III) of the spot test reaction between propranolol hydrochloride (I) and 2. The IR measurements gave a standard deviation of 0. Combining this in situ ATR approach with FTIR imaging yielded chemical images based on the spatial distribution of the absorbance of the spectral bands for corresponding excipients in the tablets. Spectra were recorded comprehensively at different points on the axially cut surface of the tablet. an increase of carbonyl index. HPMC. magnesium stearate. Water-soluble polymers are often used in tablet compaction for their desirable compaction and dissolution properties (44).013 at p = 0. then normalized and ﬁrst derivative transformed.509 and 1. (37). A quantitative IR and Raman spectroscopic approach for determination of phenacetin (Phen) and salophen (Salo) in binary solid mixtures with caffeine:phenacetin/caffeine (system 1) and salophen/caffeine (system 2) is presented (38).1% for both systems. Spectral data were recorded between 650 and 4.0513 and 0. were investigated.0507 for both systems.000 cm−1 with a 4 cm−1 resolution by FTIR spectroscopy coupled with an ATR accessory (40). A PLS calibration model for the prediction of niﬂumic acid contents was developed using 81 and 27 spectra of standard gels as training and validation sets. The methodology involving the combination spot test–diffuse reﬂectance spectroscopy offers advantages. FTIR is a useful weapon in Downloaded By: [UNICAMP] At: 23:19 1 June 2010 .3% (system 2). Absorbance ratios of 746 or 721 cm−1 peaks (characteristic for each of determined compounds in the Systems 1 and 2) to 1. A. The amounts of drug and excipient were predicted from ATR-FTIR spectra using two multiway modeling techniques. Data matrices consisted of dissolved and undissolved parallel samples having different drug content and spectra.013 and 0.214 A. respectively) were used. whereas the Raman spectroscopic data are with slightly higher conﬁdence of 99. ATR-FTIR spectroscopic imaging has been used to analyze in situ the spatial distribution of different components in tablets with different compositions. and paracetamol. hydroxypropylmethylcellulose (HPMC). parallel factor analysis (PARAFAC) and multilinear partial least squares (N-PLS) (42). Caffeine tablets made of three different polymer matrices. modiﬁcations of chemical functions are measured by FTIR (using spectrometric indices). Counterfeit drugs are becoming a serious problem because they can damage health by supplying inappropriate substances or products devoid of API.9% (system 1) and 98.
372. It has presented that IR spectra of real Cordyceps of different origins and counterfeits have their own macroscopic ﬁngerprints. a new analytical approach for the characterization and fast screening of fake and genuine artesunate tablets (47) using a combination of Raman spectroscopy. Counterfeiting can apply to both branded and generic products with counterfeit products including drugs with the correct ingredients or with the wrong ingredients. and IR and Raman spectroscopy. mannitol and polysaccharides. A scientiﬁc and systemic method for differentiation and quality estimation of a wellknown Chinese traditional medicine. In addition. During the last 5–10 years. Ginseng is an expensive herb. and intensities. American ginseng (the root of Panax quinquefolius). and 1. and Notoginseng (the root of Panax notoginseng) were differentiated by conventional Fourier transform infrared spectroscopy (1D-FTIR) and two-dimensional (2D) correlation FTIR applying a thermal perturbation (49). 1. recently. optical microscopy.048 cm−1 in the FTIR spectra among these species for their ease differentiation. thermal analysis. and adulteration with other cheaper products may occur. softgels. Downloaded By: [UNICAMP] At: 23:19 1 June 2010 . In support of the efforts to combat the illegal sale and distribution of counterfeit antimalarial drugs. Quality assurance of ginseng is needed because many of its commercial products now come in various formulations such as capsules. Through the three steps. powder. But FTIR and two-dimensional correlation infrared spectroscopy (2D-IR) are employed to propose a method for its analysis. positions. dissolution testing.640. NMR. sterols. Numerous methods have been used to measure the solid-state composition of pharmaceuticals. 1. The quality of pharmaceutical products such as ginseng is important for ensuring consumer safety and efﬁcacy (48. 49). The herbal materials of Asian ginseng (the root of Panax ginseng). The different ﬁngerprints display different chemical constitutes such as fatty acids. with insufﬁcient active ingredient or with fake packaging. (45) Some papers related to counterfeit detection using FTIR spectrometry will be brieﬂy discussed as most of the investigations reported were performed using NIR spectrometry. these include X-ray diffraction.416. The counterfeiting of pharmaceuticals has been detected since about 1990 and. 51). Many more cases are being discovered not only in the developing world but. and activity. the complementary nature of Raman scattering and FTIR imaging allowed the characterization of both the overall and surface composition of the tablets. and tea (48). deﬁnition of the crystalline phase has become as important as molecular composition in patent protection. with discriminated shapes. different Cordyceps and their counterfeits can be discriminated effectively and their qualities distinctly displayed. has not been established (46). spatially offset Raman spectroscopy (SORS). without active ingredients. nucleotides. The World Health Organization (WHO) has deﬁned counterfeit drugs as those that are deliberately mislabeled with respect to identity and/or source. particle size analysis. Changes in polymorphic form and purity often inﬂuence physical properties and pharmaceutical performance of a product (50. the problem has escalated. increasingly. and ATR-FTIR imaging. stability. variation in peak intensity was observed at about 1.FTIR in Pharmaceutical Drugs Analysis 215 rapid counterfeit detection. in developed countries. The advantages provided by a combination of SORS and ATR-FTIR imaging in this context conﬁrm its potential for inclusion in the analytical protocol for forensic investigation of counterfeit medicines. Cordyceps. Vibrational spectroscopy provided chemically speciﬁc information on the composition of the tablets. the molecular solid state has gained recognition by the pharmaceutical industry for its role in drug manufacturing. However.
Form III could be detected at similar levels by use of a signal at 1. an investigation on the behavior of the two nevirapine pseudopolymorphs through the dissolution test has been described. For this reason. Two polymorphic and a pseudopolymorphic crystal form of the local anesthetic drug hydroxyprocaine hydrochloride are characterized by spectroscopy (FTIR. and water vapor sorption analysis (52). A. and bioavailability. Estimations of polymorphic composition were carried out by correlating calculated X-ray powder diffraction (XRPD) diffractograms from Cambridge Crystallographic Data Center (CCDC) to the XRPD measurements from samples. which can affect dissolution. Identiﬁcation of risperidone polymorph A in ﬁlm coated commercial tablets was attempted using IR spectroscopy. Three different crystal forms of this non-nucleoside reverse transcriptase inhibitor were obtained after recrystallization procedures (56). besides manufacturing. Several authors (52–57) studied polymorphic forms. Furthermore. an IR method was used during process development and manufacturing of tranilast to check for phase purity in Form I (the desired form). It is obvious that FTIR spectrometry is capable of the analytical quantiﬁcation of pharmaceutical products. Identiﬁcation of the crystal phase of an active pharmaceutical ingredient in a pharmaceutical tablet is of outmost importance because different polymorphs exhibit different physicochemical properties. and XRPD (57). Crystalline product should exist in optimal polymorphic form. they can be reliably distinguished by spectroscopic methods (55). soft independent modeling of class analogy (SIMCA). and PLS together with orthogonal signal correction (OSC) techniques were utilized to characterize the polymorphic composition of bulk samples from DRIFT data (53).378 cm−1. The stability of this polymorph through time and during the manufacturing process was also examined. Nevirapine is a lipophilic drug of low aqueous solubility used in AIDS treatment. From a pharmaceutical development perspective. thermal analysis (hot stage microscopy. Raman spectroscopy. FT-Raman. diffractometric. Two new pseudopolymorphs have been characterized. SSNMR spectroscopy). Robust and reliable methods for polymorph characterization are of great importance. too: nevirapine hemihydrate and nevirapine hemiethyl acetate. multivariate statistical process control (MSPC). The presence of Form II was detectable at ca. 5% levels by observation of a band at 843 cm−1. and spectroscopic techniques. Sulfathiazole crystallization from ﬁve different mixtures of water and 1-propanol using four different constant cooling rates was studied (54). Because FTIR can be performed more rapidly and for less cost than most other techniques. Downloaded By: [UNICAMP] At: 23:19 1 June 2010 CONCLUSION The recent analytical methods in quality control of API were reviewed. Bunaciu et al.216 A. . Five polymorphic forms of tranilast were characterized by thermal. it is shown that although the anhydrous forms of tranilast have similar thermal properties. Polymorphs and pseudopolymorphs of a drug may exhibit different chemical and physical properties. powder X-ray diffractometry. stability. some of the crystal phases are protected by patents. The quality assurance of the sulfathiazole product during the whole development and manufacturing cycle of pharmaceuticals through increased level of process understanding is the main aspect to be considered within process analytical technology (PAT). and thermogravimetry). ATR-FTIR was applied for in situ concentration measurement to be able to evaluate concentration level effects to outcome of product. differential scanning calorimetry.
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