Dataset Information

A Simple and Noninvasive DOSY NMR Method for Droplet Size Measurement of Intact Oil-In-Water Emulsion Drug Products.

ABSTRACT: In a typical oil-in-water emulsion drug product, oil droplets with varied sizes are dispersed in a water phase and stabilized by surfactant molecules. The size and polydispersity of oil droplets are critical quality attributes of the emulsion drug product that can potentially affect drug bioavailability. More critically, to ensure accuracy in characterization of the finished drug product, analytical methods should introduce minimal physical perturbation (e.g., temperature variation or dilution) before the analysis. The classical methods of dynamic light scattering or electron microscopy can be used but they generally require sample dilution or harsh preparation conditions, respectively. By contrast, the size distribution of emulsion formulations can be assessed with a simple and noninvasive solution nuclear magnetic resonance method, namely, two-dimensional Diffusion Ordered SpectroscopY. The two-dimensional Diffusion Ordered SpectroscopY method probed signal decay of methyl resonances from oil and sorbate molecules and was applied to 3 types of U.S.-marketed emulsion drug products, that is, difluprednate, cyclosporine, and propofol, yielding measured droplet sizes of 40-280 nm in diameter. The high precision of ±6 nm of the new nuclear magnetic resonance method allows analytical differentiation of lot-to-lot and brand-to-brand droplet size differences in emulsion drug products, critical for drug-quality development, control, and surveillance.

SUBMITTER: Patil SM

PROVIDER: S-EPMC6995278 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A Simple and Noninvasive DOSY NMR Method for Droplet Size Measurement of Intact Oil-In-Water Emulsion Drug Products.

Patil Sharadrao M SM Li Vincent V Peng Jiangnan J Kozak Darby D Xu Jin J Cai Bing B Keire David A DA Chen Kang K

Journal of pharmaceutical sciences 20181003 2

In a typical oil-in-water emulsion drug product, oil droplets with varied sizes are dispersed in a water phase and stabilized by surfactant molecules. The size and polydispersity of oil droplets are critical quality attributes of the emulsion drug product that can potentially affect drug bioavailability. More critically, to ensure accuracy in characterization of the finished drug product, analytical methods should introduce minimal physical perturbation (e.g., temperature variation or dilution) ...[more]

PMID: 30291851

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Project description:Diffusion-ordered NMR spectroscopy (DOSY) can be used to analyze mixtures of compounds since resonances deriving from different compounds are distinguished by their diffusion coefficients (D). Previously, DOSY has mostly been used for organometallic and polymer analysis, we have now applied DOSY to investigate diffusion coefficients of structurally diverse organic compounds such as natural products (NP). The experimental Ds derived from 55 diverse NPs has allowed us to establish a power law relationship between D and molecular weight (MW) and therefore predict MW from experimental D. We have shown that D is also affected by factors such as hydrogen bonding, molar density and molecular shape of the compound and we have generated new models that incorporate experimentally derived variables for these factors so that more accurate predictions of MW can be calculated from experimental D. The recognition that multiple physicochemical properties affect D has allowed us to generate a polynomial equation based on multiple linear regression analysis of eight calculated physicochemical properties from 63 compounds to accurately correlate predicted D with experimental D for any known organic compound. This equation has been used to calculate predicted D for 217 043 compounds present in a publicly available natural product database (DEREP-NP) and to dereplicate known NPs in a mixture based on matching of experimental D and structural features derived from NMR analysis with predicted D and calculated structural features in the database. These models have been validated by the dereplication of a mixture of two known sesquiterpenes obtained from Tasmannia xerophila and the identification of new alkaloids from the bryozoan Amathia lamourouxi. These new methodologies allow the MW of compounds in mixtures to be predicted without the need for MS analysis, the dereplication of known compounds and identification of new compounds based solely on parameters derived by DOSY NMR.

Dataset Information

A Simple and Noninvasive DOSY NMR Method for Droplet Size Measurement of Intact Oil-In-Water Emulsion Drug Products.

Publications

A Simple and Noninvasive DOSY NMR Method for Droplet Size Measurement of Intact Oil-In-Water Emulsion Drug Products.

Similar Datasets

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