A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement
Loading...
Authors
Author (Corporation)
Publication date
2017
Typ of student thesis
Course of study
Collections
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Molecular Pharmaceutics
Special issue
DOI of the original publication
Link
Series
Series number
Volume
14
Issue / Number
4
Pages / Duration
1243–1250
Patent number
Publisher / Publishing institution
American Chemical Society
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
The methacrylate-copolymer Eudragit EPO (EPO) has raised interest in solubility enhancement of anionic drugs. Effects on aqueous drug solubility at rather low polymer concentrations are barely known despite their importance upon dissolution and dilution of oral dosage forms. We provide evidence for substantial enhancement (factor 4–230) of aqueous solubility of poorly water-soluble anionic drugs induced by low (0.1–5% (w/w)) concentration of EPO for a panel of seven acidic crystalline drugs. Diffusion data (determined by 1H nuclear magnetic resonance spectroscopy) indicate that the solubility increasing effect monitored by quantitative ultraperformance liquid chromatography was caused primarily by molecular API polymer interactions in the bulk liquid phase. Residual solid API remained unaltered as tested by X-ray powder diffraction. The solubility enhancement (SE) revealed a significant rank correlation (rSpearman = −0.83) with rDiffAPI, where SE and rDiffAPI are defined ratios of solubility and diffusion coefficient in the presence and absence of EPO. SE decreased in the order of indomethacin, mefenamic acid, warfarin, piroxicam, furosemide, bezafibrate, and tolbutamide. The solubilizing effect was attributed to both ionic and hydrophobic interactions between drugs and EPO. The excellent solubilizing properties of EPO are highly promising for pharmaceutical development, and the data set provides first steps toward an understanding of drug–excipient interaction mechanisms.
Keywords
acidic drugs, nuclear magnetic resonance (NMR) spectroscopy, polymer−drug interaction, solubility enhancement
Subject (DDC)
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
1543-8384
1543-8392
1543-8392
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Kirchmeyer, W., Ross, A., Wyttenbach, N., Alsenz, J., & Kuentz, M. (2017). A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement. Molecular Pharmaceutics, 14(4), 1243–1250. https://doi.org/10.1021/acs.molpharmaceut.6b01116