Departamento de Estadística e Investigación Operativa, Facultad de Farmacia, Universidad Complutense de Madrid, E-28040 Madrid, Spain.
Acta Biomater. 2010 Dec;6(12):4650-6. doi: 10.1016/j.actbio.2010.07.018. Epub 2010 Jul 17.
pH-sensitive hydrogels based on methacrylic acid (MAA) and poly(ethylene glycol) macromonomer (PEGMEMA) entrapping diltiazem hydrochloride (DIL·HCl) were synthesized inside soft gelatin capsules for use as a new dosage form for oral drug administration. Different monomer compositions were used to evaluate their swelling and release behavior in two media: at low pH, simulating the acid pH of the stomach, and at pH 7, simulating the higher pH environment of the intestine. Both the swelling process and DIL·HCl release strongly depended on pH and monomer composition. Hydrogels with intermediate compositions showed diminished DIL·HCl release at pH 1.2. This fact was related to the formation of an impermeable outer skin, observed by magnetic resonance imaging (MRI). At pH 7 similar shaped release profiles were found for the four hydrogel compositions under investigation. At this neutral pH slow protonation of the carboxylate groups of MAA led to a swelling front and a dry core, also observed by MRI. As a consequence of this anomalous swelling, release curves exhibited a long period of zero order kinetics. This shows that the system could be a suitable candidate to develop a zero order release dosage form for oral administration of DIL·HCl. The swelling and dissolution processes were analyzed by different mathematical approaches.
基于甲基丙烯酸（MAA）和聚乙二醇大分子单体（PEGMEMA）的 pH 敏感水凝胶，包埋盐酸地尔硫卓（DIL·HCl），在软明胶胶囊内合成，用作口服给药的新剂型。使用不同的单体组成来评估它们在两种介质中的溶胀和释放行为：在低 pH 值下，模拟胃的酸性 pH 值，在 pH 7 下，模拟肠的较高 pH 值环境。溶胀过程和 DIL·HCl 释放强烈依赖于 pH 值和单体组成。在 pH 1.2 时，具有中间组成的水凝胶显示出 DIL·HCl 释放的减少。这一事实与通过磁共振成像（MRI）观察到的不可渗透的外层皮肤的形成有关。在 pH 7 时，研究的四种水凝胶组成在相似的形状下释放曲线。在这种中性 pH 值下，MAA 的羧酸盐基团的缓慢质子化导致溶胀前沿和干燥核心，这也通过 MRI 观察到。由于这种异常溶胀，释放曲线表现出长时间的零级动力学。这表明该系统可能是开发用于口服 DIL·HCl 的零级释放剂型的合适候选者。通过不同的数学方法分析了溶胀和溶解过程。
