Moustafine Rouslan I, Sitenkov Alexander Y, Bukhovets Alexandra V, Nasibullin Shamil F, Appeltans Bernard, Kabanova Tatiana V, Khutoryanskiy Vitaliy V, Van den Mooter Guy
Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
Int J Pharm. 2017 May 30;524(1-2):121-133. doi: 10.1016/j.ijpharm.2017.03.053. Epub 2017 Mar 31.
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 T. DIPEC have an IR absorption band at 1560cm, 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.
评估了一种由两种带相反电荷的（甲基）丙烯酸酯共聚物（Eudragit ЕРО（EPO）和Eudragit S100（S100））组成的新型系统在口服药物递送中负载吲哚美辛（IND）的潜在应用。基于药物-聚电解质复合物（DIPEC）的颗粒（EPO-IND）/S100是通过在固定pH下混合两种共聚物的水溶液制备的。药物-聚电解质复合物（DPC）颗粒（EPO-IND）具有正的zeta电位，表明游离EPO链和与EPO序列结合的IND位于表面。通过重量法、紫外分光光度法、毛细管粘度法和元素分析确定了DPC和DIPEC的形成和组成。使用FTIR/NIR、拉曼光谱、XRPD和调制DSC研究了配制的DIPEC的结构和固态性质。DIPEC是一种化学均匀的材料，其特征在于单一的T。DIPEC在1560cm处有一个红外吸收带，可归因于与EPO的二甲氨基形成离子键的羧酸盐基团（S100，IND）的伸缩振动。XRPD、NIR和拉曼位移证实，在该制剂的制备过程中，IND转化为其无定形形式。在模拟胃肠道条件下，IND从DPC EPO/IND（3:1）和DIPEC EPO/L100/IND（4.5:1:1）中的释放是持续的，并在7小时内完成。然而，DIPEC中的S100使释放过程变慢，使该系统适用于结肠特异性递送。最后，用含吲哚美辛的DPC和DIPEC制备片剂，对于DIPEC来说，由于其吲哚美辛释放较慢，有可能用作口服剂型，适合持续递送。
