Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy

Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination...

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Veröffentlicht in:Analytical chemistry (Washington) 2023-01, Vol.95 (3), p.1880-1887
Hauptverfasser: Vanderschaeghe, Hannah, Houlleberghs, Maarten, Verheyden, Loes, Dom, Dirk, Chandran, C. Vinod, Radhakrishnan, Sambhu, Martens, Johan A., Breynaert, Eric
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container_issue 3
container_start_page 1880
container_title Analytical chemistry (Washington)
container_volume 95
creator Vanderschaeghe, Hannah
Houlleberghs, Maarten
Verheyden, Loes
Dom, Dirk
Chandran, C. Vinod
Radhakrishnan, Sambhu
Martens, Johan A.
Breynaert, Eric
description Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination is critical as the residual solvent concentration cannot exceed threshold values set by health and safety regulations (e.g., EMA/CHMP/ICH/82260/2006). For dichloromethane and methanol, for example, residual concentrations must be below 600 and 3000 ppm, respectively. Today, EU and USA Pharmacopoeias recommend tedious procedures for residual solvent quantification, requiring extraction of the solvent and subsequent quantification using capillary gas chromatography with static headspace sampling (sHS-GC). This work presents a new method based on the combination of standard addition and absolute quantification using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS qNMR). The methodology was originally developed for absolute quantification of water in zeolites and has now been validated for quantification of residual solvent in drug formations using mesoporous silica loaded with ibuprofen dissolved in DCM and MeOH as test samples. Interestingly, formulations prepared using as-received or predried mesoporous silica contained 5465 versus 484.9 ppm DCM, respectively. This implies that the initial water content of the silica carrier can impact the residual solvent concentration in drug-loaded materials. This observation could provide new options to minimize the occurrence of these undesired solvents in the final formulation.
doi_str_mv 10.1021/acs.analchem.2c03646
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source ACS Publications
subjects Bioavailability
Chemistry
Dichloromethane
Drug delivery
Formulations
Gas chromatography
Headspace
Ibuprofen
Magnetic resonance spectroscopy
Moisture content
NMR
NMR spectroscopy
Nuclear magnetic resonance
Nuclear safety
Organic solvents
Safety regulations
Silica
Silicon dioxide
Solvents
Spectroscopy
Spectrum analysis
Spinning (materials)
Water content
Zeolites
title Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy
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