Quantitative Macro-Raman Spectroscopy on Microparticle-Based Pharmaceutical Dosage Forms (original) (raw)
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Journal of pharmaceutical and biomedical analysis, 2017
A new macro-Raman system equipped with a motorized translational sample stage and low-frequency shift capabilities was developed for bulk composition and homogeneity analysis of multi-component pharmaceutical powders. Different sampling methods including single spot and scanning measurement were compared. It was found that increasing sample volumes significantly improved the precision of quantitative composition analysis, especially for poorly mixed powders. The multi-pass cavity of the macro-Raman system increased effective sample volumes by 20 times from the sample volume defined by the collection optics, i.e., from 0.02μL to about 0.4μL. A stochastic model simulating the random sampling process of polydisperse microparticles was used to predict the sampling errors for a specific sample volume. Comparison of fluticasone propionate mass fractions of the commercial products Flixotide(®) 250 and Seretide(®) 500 simulated for different sampling volumes with experimentally measured com...
2005
Dispersive Raman spectroscopy with excitation by a red diode laser is suitable for quantitative crystallinity measurements in powders for pulmonary drug delivery. In spray-dried mixtures of salmon calcitonin and mannitol, all three crystalline polymorphs of mannitol and amorphous mannitol were unambiguously identified and their mass fractions were measured with a limit of quantification of about 5%. The instrument design offered high sensitivity and adequate background suppression, resulting in a low limit of detection in the range of 0.01% to 1%. This spectroscopy method has significant advantages over established techniques regarding specificity, sensitivity, and sample requirements.
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.
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.
The AAPS Journal, 2021
Demonstrating bioequivalence (BE) of nasal suspension sprays is a challenging task. Analytical tools are required to determine the particle size of the active pharmaceutical ingredient (API) and the structure of a relatively complex formulation. This study investigated the utility of the morphologically-directed Raman spectroscopy (MDRS) method to investigate the particle size distribution (PSD) of nasal suspensions. Dissolution was also investigated as an orthogonal technique. Nasal suspension formulations containing different PSD of mometasone furoate monohydrate (MFM) were manufactured. The PSD of the MFM batches was characterized before formulation manufacture using laser diffraction and automated imaging. Upon formulation manufacture, the droplet size, single actuation content, spray pattern, plume geometry, the API dissolution rate, and the API PSD by MDRS were determined. A systematic approach was utilized to develop a robust method for the analysis of the PSD of MFM in Nason...
Low-frequency shift dispersive Raman spectroscopy for the analysis of respirable dosage forms
International journal of pharmaceutics, 2014
A high performance Raman system equipped with a CCD (charged coupled device) sensor and recently developed optical filter technology is described. It provides high sensitivity, high resolution, and access to low-frequency vibrations enabling resolution of spectral features due to lattice vibrational modes and internal vibrational modes, greatly improving the ability to detect small changes due to variations in the three dimensional molecular arrangement, e.g., during loss of crystallinity. Applications to solid state analysis, such as solid phase identification and differentiation of glycopyrronium bromide and formoterol fumarate in pharmaceutical powders, and identification of active pharmaceutical ingredients, e.g., salmeterol xinafoate, fluticasone propionate, mometasone furoate, and salbutamol sulphate, as well as excipients, e.g., amino acids, in different formulations, are presented. For the first time, low-frequency shift Raman spectra of mannitol polymorphs were measured and...
Raman Chemical Imaging for Drugs and Excipients in Aqueous Suspension Nasal Spray Formulations
Samples prepared by shaking, priming (four actuations each) and spraying each in an upright position onto inverted aluminum-coated glass microscope slides positioned approximately 6 inches from the spray nozzle. The samples were then immediately turned upright and allowed to dry. • Raman images processed to calculate PSD of active pharmaceutical ingredient (API) from 1) all API particles 2) excipient-free API particles 3) API particles adhered to other excipients. • The sizes of all PS microsphere size standards and API particles were blinded to ChemImage. Measurements and Analysis A particle size study was performed using six polystyrene (PS) microsphere size standards in order to determine the accuracy of sizing micron dimension particles using RCI and optical microscopy. To minimize systematic overestimation of particle diameter, we prepared close packed hexagonal arrays of highly uniform microspheres and measured multiple PS microspheres in an row and divided by the total number...
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 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.
Analytical Chemistry, 2012
383 tablets of a pharmaceutical product were analysed by backscatter and transmission Raman spectrometry to determine the concentration of an active pharmaceutical ingredient (API), chlorpheniramine maleate, at the 2% m/m (4 mg) level. As the exact composition of the tablets was unknown, external calibration samples were prepared from chlorpheniramine maleate and microcrystalline cellulose (Avicel) of different particle size. The API peak at 1594 cm-1 in the 2 nd derivative Raman spectra was used to generate linear calibration models. The API concentration predicted using backscatter Raman measurements was relatively insensitive to the particle size of Avicel. With transmission, however, particle size effects were greater and accurate prediction of the API content was only possible when the photon propagation properties of the calibration and sample tablets were matched. Good agreement was obtained with HPLC analysis when matched calibration tablets were used for both modes. When the calibration and sample tablets are not chemically matched, spectral normalisation based 2 on calculation of relative intensities cannot be used to reduce the effects of differences in physical properties. The main conclusion is that although better for whole tablet analysis, transmission Raman is more sensitive to differences in the photon propagation properties of the calibration and sample tablets.