Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany.
Eur J Pharm Biopharm. 2011 Oct;79(2):372-81. doi: 10.1016/j.ejpb.2011.05.001. Epub 2011 May 11.
The aim of the study was the formulation of polyelectrolyte complexes composed of poorly water-soluble acid drugs and basic polymethacrylates by hot-melt extrusion enabling a tailor-made release pattern by the addition of inorganic salts. The influence of different electrolytes was analyzed at varying conditions in order to control drug delivery from the complexes. Poorly water-soluble model drugs naproxen and furosemide were applied in their non-ionic form. After hot-melt extrusion of the naproxen-polymethacrylate powder blend, XRPD and DSC measurements indicated the formation of a single-phase amorphous system. Milled extrudates were stable under storage at long-term and intermediate conditions. Polyelectrolyte complex formation by an acid-base reaction during hot-melt extrusion could be proven by the lack of vibrations of dimethylamino and carboxylic groups by FT-IR and Raman spectroscopy. The complexes did not dissolve in demineralized water. Drug release could be immediately induced by addition of neutral electrolytes. Tailor-made dissolution profiles were realized by controlled electrolyte triggering. Maximal effects were achieved by concentrations of 0.05-0.15 M NaCl. Different anions of alkali halogenides revealed variant magnitudes of the effect depending on the anion radius. Polyelectrolyte complex formation and dissolution principles were also confirmed for furosemide.
本研究的目的是通过热熔挤出技术制备由疏水性酸药物和碱性聚甲基丙烯酸酯组成的聚电解质复合物，通过添加无机盐来实现定制的释放模式。分析了不同电解质在不同条件下的影响，以控制药物从复合物中的释放。应用非离子形式的模型药物萘普生和呋塞米。在将萘普生-聚甲基丙烯酸酯粉末混合物进行热熔挤出后，XRPD 和 DSC 测量表明形成了单相非晶态体系。研磨挤出物在长期和中期储存条件下稳定。通过傅里叶变换红外光谱和拉曼光谱证明，在热熔挤出过程中通过酸碱反应形成聚电解质复合物，其中二甲氨基和羧酸基团的振动缺失。复合物在去离子水中不溶解。通过添加中性电解质可以立即引发药物释放。通过控制电解质触发实现定制的溶解曲线。通过 0.05-0.15 M NaCl 浓度可达到最大效果。碱卤化物的不同阴离子根据阴离子半径显示出不同的效果大小。聚电解质复合物的形成和溶解原理也得到了呋塞米的证实。
