Determining the Distribution of Active Pharmaceutical Ingredients in Combination Tablets Using Near IR and Low-Frequency Raman Spectroscopy Imaging

Hisada, Hiroshi; Okayama, Akira; Hoshino, Takuya; Carriere, James; Koide, Tatsuo; Yamamoto, Yoshihiko; Fukami, Toshiro

doi:10.1248/cpb.c19-00791

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…Emerging technologies in solid-state characterization of pharmaceuticals, such as terahertz spectroscopy and low-frequency Raman (LFR) spectroscopy offer alternatives to XRPD with similar levels of sensitivity and little to no sample preparation requirement. − In recent years, numerous solid-state characterization studies have been conducted using LFR spectroscopy, including polytype identification, in situ monitoring of cocrystals, assessment of chiral purity, characterization of amorphous phases, , analysis of molecular mixing in ASDs, quantitative analysis of pigments and pharmaceutical materials, , and chemical mapping and imaging of pharmaceuticals. − LFR spectroscopy has also been utilized together with variants of Raman spectroscopy, including transmission Raman and spatially offset Raman. − Although bands in the LFR region can be challenging to utilize and analyze due to the molecular structure of the analyte or the complexity of the mixture being analyzed, LFR spectroscopy can nevertheless be beneficial when used together with conventional techniques. A detailed review on pharmaceutical applications of LFR has been published by Be̅rziņš et al…”

Section: Introductionmentioning

confidence: 99%

Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy

Hatipoglu,

Zaker,

Willett

et al. 2023

Anal. Chem.

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Two decades ago, postmarket discovery of a second crystal form of ritonavir with lower solubility had major implications for drug manufacturers and patients. Since then, ritonavir has been reformulated via the hot−melt−extrusion process in an amorphous form. Here, quantitative low-and midfrequency Raman spectroscopy methods were developed to characterize polymorphs, form I and form II, in commercial ritonavir 100 mg oral tablets as an alternate analysis approach compared to X-ray powder diffraction (XRPD). Crystallization in three lots of ritonavir products obtained from four separate manufacturers was assessed after storage under accelerated conditions at 40 °C and 75% relative humidity (RH). Results were compared with quantitative XRPD methods developed and validated according to ICH Q2 (R1) guidelines. In a four-week open-dish study, form I crystallization occurred in two of the four products and form II crystallization was detected in another ritonavir product. The limits of detection for XRPD, low-frequency Raman (LFR), and mid-frequency Raman (MFR) were determined to be 0.7, 0.8, and 0.5% for form I and 0.6, 0.6, and 1% for form II, respectively. Root-mean-squared-error of predictions were 0.6−1.0 and 0.6−2.5% for LFR-and MFR-based partial least-squares models. Further, ritonavir polymorphs could also be identified and detected directly from ritonavir tablets using transmission LFR. In summary, LFR was applied for the assessment of polymorphism in real-world samples. While providing analytical performance similar to conventional techniques, LFR reduced the single measurement time from 66 min (XRPD) to 10 s (LFR) without the need for tedious sample preparation procedures.

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Section: Introductionmentioning

confidence: 99%

Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy

Hatipoglu,

Zaker,

Willett

et al. 2023

Anal. Chem.

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“…Raman and near‐infrared (NIR) spectroscopic chemical imaging are widely used in the pharmaceutical industry for 2D chemical imaging of a tablet matrix 3–8 . The combination of microscopy and spectroscopy enables the spatial distribution of components to be easily visualised.…”

Section: Introductionmentioning

confidence: 99%

“…2 Raman and near-infrared (NIR) spectroscopic chemical imaging are widely used in the pharmaceutical industry for 2D chemical imaging of a tablet matrix. [3][4][5][6][7][8] The combination of microscopy and spectroscopy enables the spatial distribution of components to be easily visualised. Pharmaceutical applications typically involve visualising and comparing differences in the size, shape and distribution of components to monitor process changes 9,10 or understand out-of-specification (OOS) batches.…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional imaging of pharmaceutical tablets using serial sectioning and Raman chemical mapping

Carruthers

Clark

Clarke

et al. 2022

J Raman Spectroscopy

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Chemical mapping by Raman spectroscopy is widely used in the pharmaceutical industry to characterise the distribution of components within pharmaceutical tablets; however, current methods do not go beyond examining an exposed surface area of a sample. There are known limitations with estimating domain size and shape statistics from 2D chemical images as the values obtained will depend on where the domain is sectioned, potentially under‐ or overestimating its true value. The combination of Raman spectroscopic mapping and serial sectioning has been recently explored as an alternative method to obtain a depth profile of a sample; however, to date, this has involved instrumentation capable of automated Raman mapping with subsequent sample sectioning. A key requirement for Raman mapping is producing an optically flat surface, and this becomes increasingly challenging for larger surface areas required for the examination of a pharmaceutical tablet. Here, we describe 3D imaging of a tablet matrix by combining Raman mapping with independent sample sectioning to provide appropriate lateral and axial resolution. The approach was first validated by analysing a spherical object of known size and shape and comparing the 3D domain size statistics calculated from the reconstructed image to its absolute values. The method was then applied to a three‐component model system, simulating a pharmaceutical tablet, to determine the capability and applicability of the method for solid dosage formulations. The study demonstrated that relative differences in the size, shape and distribution of domains can be quantified enabling an enhanced understanding of the spatial arrangement of each component within the formulation and the effect of each processing condition on the final drug product. By visualising the 3D structure of a tablet matrix with demonstrable accuracy and precision using materials of known dimensions, new capabilities to enhance tablet manufacturing methods are now available.

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“…Raman spectroscopy and near-infrared spectroscopy have been reported as representative PAT tools. [13][14][15][16] In particular, Raman spectroscopy is a nondestructive, noncontact, and sample pretreatment-free method for characterizing molecular states. 17,18) The advantages of this technique over other PAT tools are that the water interference is minimal, 19,20) and high molecular additives have no effect on the Raman spectra.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of Cocrystal Dissociation during the Wet Granulation Process in the Presence of Disintegrants by Using Low-Frequency Raman Spectroscopy

Suzuki

Fukui

Otaka

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

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The aim of this study was to evaluate the effect of three coformers and five disintegrants in the granulation formulation on the dissociation of cocrystal during the granulation process by monitoring wet granulation with probe-type low-frequency Raman (LF-Raman) spectroscopy. As model cocrystals, paracetamol (APAP)-oxalic acid (OXA), APAP-maleic acid (MLA), and APAP-trimethylglycine (TMG) were used. The monitoring of the granulation recipe containing cocrystals during wet granulation was performed over time with high-performance LF-Raman spectrometry and the dissociation rate was calculated from the results of multivariate analysis of LF-Raman spectra. The dissociation rate decreased in the order of APAP-TMG, APAP-OXA, and APAP-MLA, showing the same order as observed in Powder X-ray diffraction measurements. Furthermore, to compare the effect of disintegrants on the dissociation rate of APAP-OXA, LF-Raman monitoring was performed for the granulation recipes containing five typical disintegrants (two lowsubstitution hydroxypropyl cellulose (HPC), cornstarch (CSW), carmellose sodium (CMC), and crospovidone (CRP)). The dissociation rate of APAP-OXA decreased in the order of CSW, HPCs, CMC, and CRP. This difference in the dissociation rate of APAP-OXA was thought to be due to the disintegration mechanism of the disintegrants and the water absorption ratio, which was expected to affect the water behavior on the disintegrant surface during wet granulation. These results suggested that probe-type LF-Raman spectroscopy is useful to monitor the dissociation behavior of cocrystals during wet granulation and can compare the relative stability of cocrystal during wet granulation between different formulations.

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Determining the Distribution of Active Pharmaceutical Ingredients in Combination Tablets Using Near IR and Low-Frequency Raman Spectroscopy Imaging

Cited by 10 publications

References 26 publications

Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy

Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy

Three‐dimensional imaging of pharmaceutical tablets using serial sectioning and Raman chemical mapping

Monitoring of Cocrystal Dissociation during the Wet Granulation Process in the Presence of Disintegrants by Using Low-Frequency Raman Spectroscopy

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