Maior João Fhilype Andrade Souto, Reis Adriano Valim, Muniz Edvani C, Cavalcanti Osvaldo Albuquerque
Laboratório de Tecnologia Farmacêutica, Programa de Pós-graduação em Ciências Farmacêuticas, Departamento de Farmácia and Farmacologia, 87020-900 Maringá, Brazil.
Int J Pharm. 2008 May 1;355(1-2):184-94. doi: 10.1016/j.ijpharm.2007.12.006. Epub 2007 Dec 23.
In this work, low-methoxyl pectin was chemically modified by reaction with glycidyl methacrylate (GMA) to give a material with low hydrosolubility. After physio-chemical characterization by FT-IR, DSC, and TGA analyses, the methacrylated/modified pectin (Pect-GMA) was crosslinked after the addition of sodium persulfate (SP), that actuates as initiator, at 50 degrees C for 24 and 48h either in the presence or not of aqueous polymethacrylate dispersion (Eudragit RS 30 D) to obtain free films by Teflon plate "casting" process. Different Pect-GMA/Eudragit RS 30 D ratios and SP concentrations were used. The free films were characterized by the determination of water vapor transmission (WVT), the swelling index (Ieq%) in simulated gastric (SGF) and intestinal (SIF) fluids, and by scanning electron microscopy (SEM). The presence of ionized groups in Pect-GMA turned the films pH-dependent because Ieq% of swollen crosslinked Pect-GMA films was larger at pH 6.8 than at pH 1.2. This was confirmed by the large pore size observed in the micrographs of SIF-swollen lyophilized films. In this way, films containing Pect-GMA and Eudragit RS 30 D, a time-dependent polymer, may present a synergistic action that favors specific biodegradation of the film in distal end of the gastrointestinal tract (GIT) by enzymes produced by the colonic microflora, enabling the modification of the release kinetics of drugs.
在本研究中,低甲氧基果胶通过与甲基丙烯酸缩水甘油酯(GMA)反应进行化学改性,得到一种低水溶性材料。通过傅里叶变换红外光谱(FT-IR)、差示扫描量热法(DSC)和热重分析(TGA)进行物理化学表征后,在添加作为引发剂的过硫酸钠(SP)后,于50℃下,在有或没有聚甲基丙烯酸水分散体(Eudragit RS 30 D)存在的情况下,将甲基丙烯酸酯化/改性果胶(Pect-GMA)交联24小时和48小时,通过聚四氟乙烯板“流延”工艺获得游离膜。使用了不同的Pect-GMA/Eudragit RS 30 D比例和SP浓度。通过测定水蒸气透过率(WVT)、在模拟胃液(SGF)和肠液(SIF)中的溶胀指数(Ieq%)以及扫描电子显微镜(SEM)对游离膜进行表征。Pect-GMA中离子化基团的存在使膜具有pH依赖性,因为交联的Pect-GMA溶胀膜在pH 6.8时的Ieq%大于在pH 1.2时的Ieq%。这通过在SIF溶胀的冻干膜显微照片中观察到的大孔径得到证实。这样,含有Pect-GMA和Eudragit RS 30 D(一种时间依赖性聚合物)的膜可能呈现协同作用,有利于结肠微生物群产生的酶在胃肠道(GIT)远端对膜进行特异性生物降解,从而能够改变药物的释放动力学。