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设计盐酸米诺环素的 pH 非依赖性缓释骨架片,用于治疗痴呆。

Design of pH-independent extended release matrix tablets of minocycline hydrochloride for the treatment of dementia.

机构信息

Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea.

出版信息

Arch Pharm Res. 2009 Nov;32(11):1593-8. doi: 10.1007/s12272-009-2112-2.

Abstract

The aim of this study was to develop a pH-independent extended release matrix tablet of minocycline HCl for the treatment of dementia. The matrix tablets were prepared by wet granulation technique using Eudragit L and S as release modifiers at different w/w ratios (1:0, 1:1 and 0:1) and PEO as a matrix former. In the case of the matrix tablet without any release modifiers, the drug release rate at pH 1.2 was much higher than that of pH 7.4. By adding the release modifier, the drug release rate at pH 7.4 increased close to that of pH 1.2 and the pH-independent release was obtained. In addition, it was shown that lubricants containing a divalent cation such as Mg stearate inhibited minocycline release in basic medium. Therefore, the incorporation of Eudragit L and S (1:1 ratio) as release modifiers and Na stearyl fumarate as a lubricant into PEO-based matrix tablets effectively produced pH-independent minocycline release profiles.

摘要

本研究旨在开发一种用于治疗痴呆症的米诺环素盐酸盐 pH 非依赖性缓释骨架片。采用湿法制粒技术,以 Eudragit L 和 S 作为释放调节剂,以不同的 w/w 比(1:0、1:1 和 0:1)和 PEO 作为基质形成剂制备骨架片。对于没有任何释放调节剂的骨架片,在 pH 1.2 时的药物释放率远高于在 pH 7.4 时的药物释放率。通过添加释放调节剂,在 pH 7.4 时的药物释放率接近 pH 1.2 时的药物释放率,从而实现了 pH 非依赖性释放。此外,还表明含有二价阳离子(如硬脂酸镁)的润滑剂会抑制米诺环素在碱性介质中的释放。因此,将 Eudragit L 和 S(1:1 比)作为释放调节剂和富马酸硬脂酸钠作为润滑剂掺入 PEO 基质骨架片中,可有效产生 pH 非依赖性米诺环素释放曲线。

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