A Novel Approach to Evaluate Amorphous-to-Crystalline Transformation of Active Pharmaceutical Ingredients in Solid Dispersion Using Time-Domain NMR

Okada, Kotaro; Hirai, Daijiro; Hayashi, Yoshihiro; Kumada, Shungo; Kosugi, Atsushi; Onuki, Yoshinori

doi:10.1248/cpb.c18-00887

Cited by 9 publications

(8 citation statements)

References 19 publications

(24 reference statements)

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“…Thus, for larger crystallites the thermodynamic equilibrium between spin system and lattice takes longer, making T 1 higher for higher crystalline samples of similar chemical structure. This effect is observed for various materials [ 26 , 27 , 28 , 29 , 30 ].…”

Section: Resultsmentioning

confidence: 85%

Features of the Gas-Permeable Crystalline Phase of Poly-2,6-dimethylphenylene Oxide

et al. 2021

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Poly-2,6-dimethylphenylene oxide (PPO) film samples with varying degrees of crystallinity (from 0 to 69%) were obtained by means of different techniques. The films were studied by various physicochemical methods (Fourier-transform infrared spectroscopy, positron annihilation lifetime spectroscopy, X-ray diffraction, and 1H nuclear magnetic resonance relaxation). Solubility coefficients of gases in the PPO samples were measured via sorption isotherms of gases by volumetric technique with chromatographic detection. The apparent activation energy of permeation and the activation energy of diffusion of all gases were estimated based on temperature dependences of gas permeability and diffusivity for amorphous and semi-crystalline PPO in the range of 20–50 °C. The peculiarities of free volume, density, and thermal properties of gas transport confirm the nanoporosity of the gas-permeable crystalline phase of PPO. So, the PPO can be included in the group of organic molecular sieves.

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Section: Resultsmentioning

confidence: 85%

Features of the Gas-Permeable Crystalline Phase of Poly-2,6-dimethylphenylene Oxide

et al. 2021

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“…To date, measuring NMR relaxation can evaluate the crystalline state of drug powder. [16][17][18][19] While the drug molecule has protons, silica has few protons; therefore, the crystalline state of the drug-loaded silica can be evaluated by 1 H-NMR relaxation. In the present study, NMR relaxation was measured using low-field time-domain NMR (TD-NMR).…”

Section: Introductionmentioning

confidence: 99%

Low-Field NMR to Characterize the Crystalline State of Ibuprofen Confined in Ordered or Nonordered Mesoporous Silica

Okada

Hayashi

Tsuji

et al. 2022

CHEMICAL & PHARMACEUTICAL BULLETIN

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The crystalline state of ibuprofen (IBU) confined in mesoporous silica was characterized using low-field time-domain nuclear magnetic resonance (TD-NMR). IBU was loaded into ordered (Santa Barbara Amorphous-15 [SBA-15]; SBA) or nonordered mesoporous silica (Sylysia 320; SYL) using a well-known incipient wetness impregnation method. The dissolution profile of IBU from the silica was measured. The IBU-loaded SBA showed a relatively higher drug concentration at 10 and 20 min, which was typical of a supersaturated solution. However, it did not maintain that concentration. By contrast, the IBU-loaded SYL did not show such a dissolution profile in the early stage. To characterize the crystalline state of IBU confined in silica, the T 1 relaxation time of IBU-loaded silica powder was measured and analyzed by curve fitting. Monophasic T 1 relaxation was observed for IBU-loaded SBA. This may indicate that the amorphous phase, which has various molecular mobilities, was close to within the length of 1 H spin diffusion. The TD-NMR technique, even if the sample is powder, can rapidly and easily measure NMR relaxation. Therefore, it can be useful toward fully characterizing the crystalline state of drugs confined in mesopores.

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“…Time domain-NMR (TD-NMR) over the years has been proven to be a valuable tool to carry out experiments upon relaxation analysis of heterogeneous solid samples. − Recently, a method has been proposed to use TD-NMR to reveal the amorphous content in mixed drug samples. According to this approach, quantitation of different solid forms in binary mixtures could be achieved by exploiting the different species’ longitudinal relaxation times ( T 1 ) registered in a saturation recovery curve (SRC), hence the name quantitative saturation recovery curve (qSRC). − …”

Section: Introductionmentioning

confidence: 99%

Quantitation of Commercially Available API Solid Forms by Application of the NMR-qSRC Approach: An Optimization Strategy Based on In Silico Simulations

et al. 2021

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Physical forms of active pharmaceutical ingredients (APIs) play a crucial role in drug discovery since 85% of API molecules exhibit polymorphism and sometimes complicated phase behavior, often resulting in important differences in the respective biochemical and physical properties. Characterization and quantitation of the different forms are becoming more and more essential in the pharmaceutical industry: once these characteristics are known, it is easier to choose the best solid form for development, formulation, manufacturing, and storage. Time domain-nuclear magnetic resonance (TD-NMR) has recently been used to develop a quantitation protocol for solid mixtures, named qSRC, based on the linear combination of T 1 saturation recovery curves (SRCs) collected on a bench-top instrument. Despite its potentials and ease of use, a limited number of application cases have been reported in the literature since its development and many aspects remain to be clarified for the technique to be adopted as a robust routinely industrial analytical tool. In the present work, the reliability of the qSRC approach has been studied by focusing on the role played by key experimental variables, including mixture composition, signal-to-noise ratio, and T 1 differences. In silico simulations were carried out for a wide range of theoretical cases to predict the expected level of accuracy obtainable for a given sample-parameter acquisition set and to clearly define the range of applicability of the method. Results of the simulation are presented alongside a comparison with three real-case studies of commercially available APIs: piroxicam, naproxen sodium, and benzocaine.

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A Novel Approach to Evaluate Amorphous-to-Crystalline Transformation of Active Pharmaceutical Ingredients in Solid Dispersion Using Time-Domain NMR

Cited by 9 publications

References 19 publications

Features of the Gas-Permeable Crystalline Phase of Poly-2,6-dimethylphenylene Oxide

Features of the Gas-Permeable Crystalline Phase of Poly-2,6-dimethylphenylene Oxide

Low-Field NMR to Characterize the Crystalline State of Ibuprofen Confined in Ordered or Nonordered Mesoporous Silica

Quantitation of Commercially Available API Solid Forms by Application of the NMR-qSRC Approach: An Optimization Strategy Based on In Silico Simulations

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