Department of Pharmaceutics, Ghent University, Ghent, Belgium.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1206-14. doi: 10.1016/j.ejpb.2013.01.027. Epub 2013 Feb 26.
Polymethacrylates such as Eudragit® polymers are well established as drug delivery matrix. Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization. These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets. Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit. These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties. The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics. Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding.
聚甲基丙烯酸酯如 Eudragit®聚合物已被广泛应用于药物传递基质。在这里，我们通过自由基聚合合成了几种 Eudragit E PO（正丁基、二甲基氨基乙基、甲基-甲基丙烯酸酯三元共聚物）类似物。这些聚合物通过热熔挤出进行加工，然后通过注塑成型进行评估，用作生产速释固体溶液片剂的载体。三种化学修饰方法增加了聚合物的玻璃化转变温度：（a）用叔丁基取代正丁基，（b）降低二甲基氨基乙基甲基丙烯酸酯（DMAEMA）的含量，以及（c）引入大体积异冰片基重复单元。这些结构修饰表明，通过改变聚合物的 Tg 可以提高片剂的机械稳定性，而不影响药物释放特性和玻璃态固体溶液形成特性。DMAEMA 单元的存在对于 API/聚合物相互作用（在形成玻璃态固体溶液中至关重要）和药物释放特性至关重要。此外，这些化学修饰强调了需要通过热熔挤出和注塑成型更合理地设计（甲基丙烯酸酯）聚合物基质赋形剂用于药物制剂。
