title: Indomethacin-containing interpolyelectrolyte complexes based on Eudragit®E PO/S 100 copolymers as a novel drug delivery system.
abstract: Potential applications of a novel system composed of two oppositely-charged (meth)acrylate copolymers, Eudragit®ЕРО (EPO) and Eudragit®S100 (S100), loaded with indomethacin (IND) in oral drug delivery were evaluated. The particles based on drug-interpolyelectrolyte complexes (DIPEC), (EPO-IND)/S100, were prepared by mixing aqueous solutions of both copolymers at fixed pH. Particles of drug-polyelectrolyte complex (DPC), (EPO-IND) have a positive zeta potential, pointing to the surface location of free EPO chains and IND bound to EPO sequences. The formation and composition of both DPC and DIPEC were established by gravimetry, UV-spectrophotometry, capillary viscosity and elemental analysis. The structure and solid state properties of the formulated DIPEC were investigated using FTIR/NIR, Raman spectroscopy, XRPD and modulated DSC. DIPEC is a chemically homogenous material, characterized by a single Tg. DIPEC have an IR absorption band at 1560cm-1, which can be assigned to the stretching vibration of the carboxylate groups (S100, IND) that form ionic bonds with the dimethylamino groups of EPO. XRPD, NIR and Raman-shifts confirm that during the preparation of this formulation, IND is converted into its amorphous form. The release of IND from DPC EPO/IND (3:1) and DIPEC EPO/L100/IND (4.5:1:1) is sustained and is completed within 7h under GIT mimicking conditions. However, S100 within DIPEC makes the release process slower making this system suitable for colon-specific delivery. Finally, DPC and DIPEC with indomethacin were used to prepare tablets, which can be potentially used as oral dosage forms for their slower indomethacin release in case of DIPEC which could be suitable for sustained delivery.
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation. Electronic address: rouslan.moustafine@gmail.com.
authors.forename: Rouslan I
authors.initials: RI
authors.lastname: Moustafine
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Sitenkov
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Bukhovets
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
authors.forename: Shamil F
authors.initials: SF
authors.lastname: Nasibullin
authors.affiliation: Drug Delivery and Disposition, University of Leuven (KU Leuven), Leuven, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Appeltans
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Kabanova
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG66AD, Berkshire, United Kingdom.
authors.forename: Vitaliy V
authors.initials: VV
authors.lastname: Khutoryanskiy
authors.affiliation: Drug Delivery and Disposition, University of Leuven (KU Leuven), Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility
chemical_list: D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C518398:Eudragit E PO; D007213:Indomethacin
keywords: Drug-interpolyelectrolyte complexes; Drug-polyelectrolyte complexes; Eudragit(®) EPO; Eudragit(®) S100; Indomethacin; Oral drug delivery