Indomethacin-containing 1 interpolyelectrolyte complexes based on 2 Eudragit ® E PO / S 100 copolymers as a 3 novel drug delivery system 4

14 Potential applications of a novel system composed of two oppositely-charged (meth)acrylate 15 copolymers, Eudragit ЕРО (EPO) and Eudragit S100 (S100), loaded with indomethacin (IND) in 16 oral drug delivery were evaluated. The particles based on drug-interpolyelectrolyte complexes 17 (DIPEC), (EPO-IND)/S100, were prepared by mixing aqueous solutions of both copolymers at fixed 18 pH. Particles of drug-polyelectrolyte complex (DPC), (EPO-IND) have a positive zeta potential, 19 pointing to the surface location of free EPO chains and IND bound to EPO sequences. The 20 formation and composition of both DPC and DIPEC were established by gravimetry, UV21 spectrophotometry, capillary viscosity and elemental analysis. The structure and solid state 22 properties of the formulated DIPEC were investigated using FTIR/NIR, Raman spectroscopy, XRPD 23 and modulated DSC. DIPEC is a chemically homogenous material, characterized by a single Tg. 24 DIPEC have an IR absorption band at 1560 cm, which can be assigned to the stretching vibration of 25 the carboxylate groups (S100, IND) that form ionic bonds with the dimethylamino groups of EPO. 26 XRPD, NIR and Raman-shifts confirm that during the preparation of this formulation, IND is 27 converted into its amorphous form. The release of IND from DPC EPO/IND (3:1) and DIPEC 28 EPO/L100/IND (4.5:1:1) is sustained and is completed within 7 hours under GIT mimicking 29 conditions. However, S100 within DIPEC makes the release process slower making this system 30 suitable for colon-specific delivery. Finally, DPC and DIPEC with indomethacin were used to 31 prepare tablets, which can be potentially used as oral dosage forms for their slower 32 indomethacin release in case of DIPEC which could be suitable for sustained delivery. 33