Quinteros Daniela Alejandra, Allemandi Daniel Alberto, Manzo Ruben Hilario
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, CP 5000, Argentina.
Sci Pharm. 2012 Apr-Jun;80(2):487-96. doi: 10.3797/scipharm.1107-17. Epub 2012 Apr 30.
Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH)(50) (HCl)(50)) having fifty mole percent of each counterion (A(-) and Cl(-)) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH(3))CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH(2)-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from -(CH(3))CH-COOH complexes were clearly higher than those of -CH(2)-COOH ones.
本研究报道了由一组五种非甾体抗炎药（AH）与阳离子聚甲基丙烯酸酯Eudragit E 100（EU）络合而成的水性体系的平衡和释放特性。含有每种抗衡离子（A⁻和Cl⁻）各五十摩尔百分比的组合物（EU(AH)(50) (HCl)(50)）可产生澄清、稳定的水性分散体，其中相当高比例（高于98%）的AH以离子对的形式与PE缩合。这一特性扩展了AH可溶于水的pH区间。该组AH包括含有和不含有α-甲基的成员（-(CH(3))CH-COOH：氟比洛芬、萘普生、酮洛芬）和（-CH(2)-COOH：双氯芬酸、吲哚美辛）。前一组络合物中离子对的比例较低。在Franz扩散池（Franz cells）中测定了AH从络合物向盐溶液（0.9% NaCl）的释放。这五种络合物表现为药物载体，呈现出缓慢的药物释放且具有显著的零级释放特性。与观察到的抗衡离子缩合百分比一致，-(CH(3))CH-COOH络合物的释放速率明显高于-CH(2)-COOH络合物。
