Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders (original) (raw)
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Quantitative Macro-Raman Spectroscopy on Microparticle-Based Pharmaceutical Dosage Forms
Applied Spectroscopy, 2015
Quantitative macro-Raman spectroscopy was applied to the analysis of the bulk composition of pharmaceutical drug powders. Powders were extracted from seven commercial lactose-carrierbased dry-powder inhalers: Flixotide 50, 100, 250, and 500 lg/dose (four concentrations of fluticasone propionate) and Seretide 100, 250, and 500 lg/dose (three concentrations of fluticasone propionate, each with 50 lg/dose salmeterol xinafoate). Also, a carrierfree pressurized metered-dose inhaler of the same combination product, Seretide 50 (50 lg fluticasone propionate and 25 lg salmeterol xinafoate per dose) was tested. The applicability of a custom-designed dispersive macro-Raman instrument with a large sample volume of 0.16 lL was tested to determine the composition of the multicomponent powder samples. To quantify the error caused by sample heterogeneity, a Monte Carlo model was developed to predict the minimum sample volume required for representative sampling of potentially heterogeneous samples at the microscopic level, characterized by different particle-size distributions and compositions. Typical carrier-free respirable powder samples required a minimum sample volume on the order of 10 À4 lL to achieve representative sampling with less than 3% relative error. In contrast, dosage forms containing non-respirable carriers (e.g., lactose) required a sample volume on the order of 0.1 lL for representative measurements. Error analysis of the experimental results showed good agreement with the error predicted by the simulation.
Raman spectroscopy for quantitative analysis of pharmaceutical solids
Journal of Pharmacy and Pharmacology, 2007
Raman spectroscopy is experiencing a surge in interest in solid-state pharmaceutical applications. It is rapid, non-destructive, no sample preparation is required and measurements can be made in aqueous environments. It can be used for not only qualitative, but also quantitative, analysis. In this paper, the use of Raman spectroscopy for quantitative analysis of pharmaceutical solids is reviewed. The technique has been used for chemical and physical form analysis. Physical form analysis has involved quantification of polymorphism, hydrates, the amorphous form and, recently, protein conformation. Initially, simple powder systems were quantified, although this has since extended to complex pharmaceutical formulations, including tablets, capsules, microspheres and suspensions. Formulations have also been analysed through packaging. The characteristics of the technique make it ideal for process monitoring and it has been used to quantify changes in-situ during processes such as wet gran...
Journal of Pharmaceutical and Biomedical Analysis, 2011
A detailed characterisation of the performance of transmission Raman spectroscopy was performed from the standpoint of rapid quantitative analysis of pharmaceutical capsules using production relevant formulations comprising of active pharmaceutical ingredient (API) and 3 common pharmaceutical excipients. This research builds on our earlier studies that identified the unique benefits of transmission Raman spectroscopy compared to conventional Raman spectroscopy. These include the ability to provide bulk information of the content of capsules, thus avoiding the sub-sampling problem, and the suppression of interference from the capsule shell. This study demonstrates, for the first time, the technique's insensitivity to the amount of material held within the capsules. Different capsules sizes with different overall fill weights (100-400 mg) and capsule shell colours were assayed with a single calibration model developed using only one weight and size sample set (100 mg) to a relative error of typically <3%. The relative root mean square error of prediction of the concentration of API for the main sample set (nominal content 75%, w/w) was 1.5% with a 5 s acquisition time. Models built using the same calibration set also predicted the 3 low level excipients with relative errors of 5-15%. The quantity of API was also predicted (with a relative error within ∼3%) using the same model for capsules prepared with different generations of API (i.e. API manufactured via different processes). The study provides further foundation blocks for the establishment of this emerging technique as a routine pharmaceutical analysis tool, capitalising on the inherently high chemical specificity of Raman spectroscopy and the non-invasive nature of the measurement. Ultimately, this technique has significant promise as a Process Analytical Technology (PAT) tool for online production application.
Journal of Raman Spectroscopy, 2020
Raman microimaging, as a product of Raman microspectroscopy mapping and multivariate analysis, was used for the localization and quantification of active pharmaceutical ingredients (APIs) in tablets made in laboratory. This was done to develop an analytical strategy to simultaneously recover qualitative and quantitative information of solid dosage forms at a microscopic level by using a nondestructive method. A chemical system, composed of acetaminophen (AMP), caffeine, and one excipient (microcrystalline cellulose), was subjected to chemometric analysis through principal component analysis (PCA) and multivariate curve resolution with alternating least squares (MCR-ALS). This was done by using Raman spectra obtained from microscopic images with pixel sizes of 15 × 15 μm to localize the APIs in the tablets. Partial least squares (PLS) was applied as a calibration method to obtain bulk and single-pixel concentrations of APIs in the samples. MCR-ALS provided better results than PCA for the localization of APIs. PLS achieved satisfactory root mean standard error values in the external validation set (<4% w/w) in bulk concentration determinations of AMP. This method also achieved concentrations for each pixel of the images, reconstructing images very similar to those obtained by MCR-ALS. Consequently, simultaneous localization and quantification of AMP was possible. Finally, the performance of Raman microimaging was evaluated through estimation of analytical figures of merit (AFOMs) of the technique used to assess the quantification of APIs. This included different calculus of uncertainty in the signal in a technique where the signal/noise ratio is low, and AFOMs for multivariate quantification are not often reported.
Drug Characterization in Low Dosage Pharmaceutical Tablets Using Raman Microscopic Mapping
Applied Spectroscopy, 2006
Raman micro-spectroscopic mapping is utilized to analyze pharmaceutical tablets containing a low concentration (0.5% w/w) of active pharmaceutical ingredient (API). The domain sizes and spatial distributions of the API and the major excipients are obtained. Domain size of the API is found to be dependent upon the particle size distribution of the ingoing API material, making the Raman maps good indicators of the source of API used in tablet manufacturing. Multivariate classification was performed to simultaneously check for the presence of two undesired API polymorphs within tablets. Raman mapping was demonstrated capable of detecting in the tablet matrix as little as 10% form conversion of the low-dosage (0.5% w/w) API, which is equivalent to detection of a 0.05% w/w polymorphic impurity. Overall, the information provided by Raman micro-spectroscopic mapping was found to have potential utility for manufacturing process optimization or predictive stability assessments.
Handheld spectrophotometers Raman spectroscopy Spatially offset Raman scattering comparison of quantitative performances Quantitation through packaging A B S T R A C T Handheld Raman spectroscopy is actually booming. Recent devices improvements aim at addressing the usual Raman spectroscopy issues: fluorescence with shifted-excitation Raman difference spectroscopy (SERDS), poor sensitivity with surface enhanced Raman scattering (SERS) and information only about the sample surface with spatially offset Raman spectroscopy (SORS). While qualitative performances of handheld devices are generally well established, the quantitative analysis of pharmaceutical samples remains challenging.
Applied spectroscopy, 2017
Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was inves...
Raman spectroscopy as a PAT for pharmaceutical blending: Advantages and disadvantages
Journal of pharmaceutical and biomedical analysis, 2018
Raman spectroscopy has been positively evaluated as a tool for the in-line and real-time monitoring of powder blending processes and it has been proved to be effective in the determination of the endpoint of the mixing, showing its potential role as process analytical technology (PAT). The aim of this study is to show advantages and disadvantages of Raman spectroscopy with respect to the most traditional HPLC analysis. The spectroscopic results, obtained directly on raw powders, sampled from a two-axis blender in real case conditions, were compared with the chromatographic data obtained on the same samples. The formulation blend used for the experiment consists of active pharmaceutical ingredient (API, concentrations 6.0% and 0.5%), lactose and magnesium stearate (as excipients). The first step of the monitoring process was selecting the appropriate wavenumber region where the Raman signal of API is maximal and interference from the spectral features of excipients is minimal. Blend ...
A REVIEW STUDY ON RAMAN SPECTROMETER AND ITS APPLICATION IN PHARMACEUTICAL INDUSTRIES
Trans stellar Journals, 2021
Raman spectroscopy is a vibrational spectroscopic approach for easily interpreting and structurally identifying tiny quantities of compounds, solids, liquids, and gases based on their distinct vibrational properties. The purpose of this study is to provide an overview of Raman spectrometers in the field of pharmaceutical analysis. How has the development of the Raman spectrometer aided the pharmaceutical industry? Detection of a wide range of placebos, medications, substances, and their structures. How do they feel about the characteristics following the reaction? This spectroscopic method is used for qualitative and quantitative analysis of trace amounts of counterfeit drugs and other illegal substances on various matrices in a non-destructive manner without extensive sample preparation. This paper also describes Raman spectroscopy, its types, and its major applications. This study also includes a brief overview of Raman spectroscopy, including theoretical approaches, evolution, and numerous techniques, which are utilized for various studies. The field of light collecting and suitable source selection for the application is at the heart of the Raman spectrometer. How may the source and its accompanying optics be beneficial for the application in question? The report also proposes research to improve and develop the flexible low-cost Raman in the pharmaceutical industry, particularly for illegal substance analysis. The Raman spectroscopy method is based on the inelastic scattering of light by materials. Light scatters in two different ways: elastically and in elastically. Where the wavelengths of scattered light are the same and different. By detecting that one can offer the structural information about the samples, the wavelength shift describes the energy transfer from one incoming photon to the molecules of the sample.