Tailor-made release triggering from hot-melt extruded complexes of basic polyelectrolyte and poorly water-soluble drugs

被引：33

作者：

Kindermann, Christoph ^{[1
]}

Matthee, Karin ^{[1
]}

Strohmeyer, Jutta ^{[2
]}

Sievert, Frank ^{[2
]}

Breitkreutz, Joerg ^{[1
]}

机构：

[1] Univ Dusseldorf, Inst Pharmaceut & Biopharmaceut, D-40225 Dusseldorf, Germany

[2] Ratiopharm GmbH, Ulm, Germany

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2011年 / 79卷 / 02期

关键词：

Polyelectrolyte complex; Hot-melt extrusion; Acid-base reaction; Electrolyte triggering; Tailor-made dissolution; HIGHLY AGGREGATING SYSTEMS; SOLID DOSAGE FORMS; RAMAN-SPECTROSCOPY; INTERPOLYELECTROLYTE COMPLEXES; SOLUBILITY PARAMETERS; DELIVERY TECHNOLOGY; EXTRUSION; MECHANISM; POLYMERS; SALT;

D O I：

10.1016/j.ejpb.2011.05.001

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：372 / 381

页数：10