A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

Nie, Haichen; Klinzing, Gerard R.; Xu, Wei

doi:10.1016/j.ijpharm.2022.121608

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…The chemometric model was successfully deployed to monitor OABA form II conversion to form I in a supersaturated solution. Similar calibration procedures for monitoring solid form conversion have been reported in the literature for both aqueous and tablet systems, including a recent study by Nie et al [ 17 ] at Merck. The authors created both reflectance and transmission Raman models for monitoring pioglitazone hydrochloride salt (PIO-HCl) as it disproportionated to its free base form in tablets at different stress conditions (40 °C/75% RH and 40 °C/35% RH).…”

Section: Introductionmentioning

confidence: 85%

“…Raman spectroscopy is commonly used as a PAT tool in the pharmaceutical industry to monitor salt formation and disproportionation during drug substance and product development [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. This spectroscopic tool is a light scattering technique that induces changes in molecular vibrations and rotational energies associated with the polarizability of the sample.…”

Section: Introductionmentioning

confidence: 99%

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Developing In Situ Chemometric Models with Raman Spectroscopy for Monitoring an API Disproportionation with a Complex Polymorphic Landscape

Mohan

Chu³

et al. 2023

Pharmaceuticals

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An in situ Raman method was developed to characterize the disproportionation of two salts involving a complex polymorphic landscape comprising up to two metastable and one stable freebase forms. Few precedents exist for Raman calibration procedures for solid form quantitation involving more than two polymorphs, while no literature examples were found for cases with multiple metastable forms. Therefore, a new Raman calibration procedure was proposed by directly using disproportionation experiments to generate multiple calibration samples encompassing a range of polymorph ratios through in-line Raman measurements complemented by off-line reference X-ray diffraction measurements. The developed Raman methods were capable of accurately quantitating each solid form in situ when solid concentration variation was incorporated into the calibration dataset. The kinetic understanding of the thermodynamically driven polymorphic conversions gained from this Raman method guided the selection of the salt best suited for the delivery of the active ingredient in the drug product. This work provided a spectroscopic and mathematical approach for simultaneously quantitating multiple polymorphs from a complex mixture of solids with the objective of real-time monitoring.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Developing In Situ Chemometric Models with Raman Spectroscopy for Monitoring an API Disproportionation with a Complex Polymorphic Landscape

Mohan

Chu³

et al. 2023

Pharmaceuticals

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“…SIMCA (version 13.0.3, Umetrics-Sartorius Data Analytics) was used to process PDF and ssNMR data for PCA. The total PDF pattern and ssNMR spectra were pretreated by standard normal variate transformation as the centering and autoscaling approach, as described previously. , …”

Section: Methodsmentioning

confidence: 99%

“…The total PDF pattern and ssNMR spectra were pretreated by standard normal variate transformation as the centering and autoscaling approach, as described previously. 10,56 3. RESULTS…”

mentioning

confidence: 99%

Probing Molecular Packing of Amorphous Pharmaceutical Solids Using X-ray Atomic Pair Distribution Function and Solid-State NMR

Chen,

Nie,

Benmore

et al. 2023

Mol. Pharmaceutics

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The structural investigation of amorphous pharmaceuticals is of paramount importance in comprehending their physicochemical stability. However, it has remained a relatively underexplored realm primarily due to the limited availability of high-resolution analytical tools. In this study, we utilized the combined power of X-ray pair distribution functions (PDFs) and solid-state nuclear magnetic resonance (ssNMR) techniques to probe the molecular packing of amorphous posaconazole and its amorphous solid dispersion at the molecular level. Leveraging synchrotron X-ray PDF data and employing the empirical potential structure refinement (EPSR) methodology, we unraveled the existence of a rigid conformation and discerned short-range intermolecular C−F contacts within amorphous posaconazole. Encouragingly, our ssNMR 19 F− 13 C distance measurements offered corroborative evidence supporting these findings. Furthermore, employing principal component analysis on the X-ray PDF and ssNMR data sets enabled us to gain invaluable insights into the chemical nature of the intermolecular interactions governing the drug−polymer interplay. These outcomes not only furnish crucial structural insights facilitating the comprehension of the underlying mechanisms governing the physicochemical stability but also underscore the efficacy of synergistically harnessing X-ray PDF and ssNMR techniques, complemented by robust modeling strategies, to achieve a high-resolution exploration of amorphous structures.

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Effect of Material Properties and Variability of Mannitol on Tablet Formulation Development

2023

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A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

Cited by 8 publications

References 44 publications

Developing In Situ Chemometric Models with Raman Spectroscopy for Monitoring an API Disproportionation with a Complex Polymorphic Landscape

Developing In Situ Chemometric Models with Raman Spectroscopy for Monitoring an API Disproportionation with a Complex Polymorphic Landscape

Probing Molecular Packing of Amorphous Pharmaceutical Solids Using X-ray Atomic Pair Distribution Function and Solid-State NMR

Effect of Material Properties and Variability of Mannitol on Tablet Formulation Development

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