Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release
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Publication date
04/2018
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01A - Journal article
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Parent work
European Journal of Pharmaceutics and Biopharmaceutics
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Volume
125
Issue / Number
Pages / Duration
68-75
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Elsevier
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Abstract
Recent work demonstrated remarkable solubilization effects of methacrylate-copolymer Eudragit EPO (EPO) not only with acidic drugs but interestingly also with poorly soluble basic compounds. The current work studied EPO-mediated solubilization effects first in vitro using felodipine (FLP) and tamoxifen (TMX) as model compounds. EPO-containing solutions were subsequently compared in a rat pharmacokinetic study against reference solutions and suspensions. Surprisingly, solution formulations with EPO did not result in an increased relative oral bioavailability. Exposure was reduced for both drugs and plasma-profiles of the EPO solutions showed a delayed and lower maximum plasma concentration compared to the reference formulations. This sustained in vivo release was likely due to combined effects of strong drug-polymer interactions and pH-dependent precipitation of the polymer in the rat intestine. Remarkable was that in vitro drug-polymer coprecipitates did not reveal crystalline drug by polarized light microscopy. Thus, such a formulation approach provides a rather simple opportunity to modify drug release in vivo. However, this may be rather an approach for preclinical formulations, if high peak-to-trough ratios of plasma levels are problematic regarding adverse effects related to Cmax or if plasma concentrations drop too fast below required pharmacological concentrations
Keywords
solubility enhancement, polymer drug interaction, Oral bioavailability, sustained release
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0939-6411
1873-3441
1873-3441
Language
English
Created during FHNW affiliation
Yes
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Published
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Peer review of the complete publication
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Citation
Saal, W., Wyttenbach, N., Alsenz, J., & Kuentz, M. (2018). Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release. European Journal of Pharmaceutics and Biopharmaceutics, 125, 68–75. https://doi.org/10.1016/j.ejpb.2018.01.006