Vaghani Subhash S, Patel Madhabhai M
Jodhpur National University, Rajasthan, India.
Curr Drug Discov Technol. 2011 Jun;8(2):126-35. doi: 10.2174/157016311795563848.
The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for repaglinide. The hydrogels were synthesised by crosslinking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 95% loading of repaglinide. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling was found due to the protonation of a primary amino group on chitosan. In acidic condition chitosan was ionized, and adhesion occurred between the positively charged chitosan and the negatively charged mucus. In the physiological condition less swelling was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 14:6 w/w showed complete drug release after 12h. Release profile showed that all the formulations followed non-fickian diffusion mechanism (diffusion coupled with swelling). Fourier transform infrared (FTIR) spectroscopic analysis revealed proper crosslinking of polymer and formation of semi-IPN as well as presence of drug in the formulation. Differential scanning calorimetry (DSC) and powder x-ray diffraction (p-XRD) study revealed the presence of repaglinide in crystalline form in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which indicated generation of open channel-like structure in hydrogel after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of repaglinide in acidic environment.
本研究的目的是开发一种基于pH敏感型壳聚糖/聚乙烯吡咯烷酮（PVP）的瑞格列奈控释给药系统。通过戊二醛交联壳聚糖和PVP共混物合成水凝胶，形成半互穿聚合物网络（semi-IPN）。对这些半互穿聚合物网络进行了含量均匀度、溶胀指数（SI）、粘膜粘附性、润湿性、体外释放及其释放动力学的研究。水凝胶对瑞格列奈的载药量超过95%。这些水凝胶在酸性条件下表现出高溶胀性和粘膜粘附性。溶胀是由于壳聚糖上伯氨基的质子化。在酸性条件下，壳聚糖发生离子化，带正电荷的壳聚糖与带负电荷的粘液之间发生粘附。在生理条件下，溶胀较小。体外释放研究表明，壳聚糖（2% w/v）和PVP（4% w/v）比例为14:6 w/w的制剂在12小时后药物完全释放。释放曲线表明，所有制剂均遵循非菲克扩散机制（扩散与溶胀耦合）。傅里叶变换红外（FTIR）光谱分析表明聚合物交联适当，形成了半互穿聚合物网络，并且制剂中存在药物。差示扫描量热法（DSC）和粉末X射线衍射（p-XRD）研究表明制剂中存在结晶形式的瑞格列奈。研究了半互穿聚合物网络在模拟胃液（SGF，pH 1.2）中溶解前后的表面形态，结果表明水凝胶溶解后形成了开放通道状结构。研究结果表明，壳聚糖/PVP半互穿聚合物网络是在酸性环境中递送瑞格列奈的有力候选物。
