Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release

dc.accessRightsAnonymous
dc.audienceScience
dc.contributor.authorSaal, Wiebke
dc.contributor.authorWyttenbach, Nicole
dc.contributor.authorAlsenz, Jochem
dc.contributor.authorKuentz, Martin
dc.date.accessioned2018-12-14T15:42:44Z
dc.date.available2018-12-14T15:42:44Z
dc.date.issued2018-04
dc.description.abstractRecent 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
dc.identifier.doi10.1016/j.ejpb.2018.01.006
dc.identifier.issn0939-6411
dc.identifier.issn1873-3441
dc.identifier.urihttp://hdl.handle.net/11654/26983
dc.language.isoen
dc.publisherElsevieren_US
dc.relation.ispartofEuropean Journal of Pharmaceutics and Biopharmaceuticsen_US
dc.subjectsolubility enhancement
dc.subjectpolymer drug interaction
dc.subjectOral bioavailability
dc.subjectsustained release
dc.titleInteractions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release
dc.type01A - Beitrag in wissenschaftlicher Zeitschrift
dc.volume125
dspace.entity.typePublication
fhnw.InventedHereYes
fhnw.IsStudentsWorkno
fhnw.PublishedSwitzerlandNo
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.affiliation.hochschuleHochschule für Life Sciencesde_CH
fhnw.affiliation.institutInstitut für Pharma Technologyde_CH
fhnw.pagination68-75
fhnw.publicationOnlineJa
fhnw.publicationStatePublished
relation.isAuthorOfPublication68819448-8611-488b-87bc-1b1cf9a6a1b4
relation.isAuthorOfPublication.latestForDiscovery68819448-8611-488b-87bc-1b1cf9a6a1b4
Dateien