Belgamwar Veena Shailendra, Surana Sanjay Javerilal
Department of Pharmaceutics, RC Patel Institute of Pharmaceutical Education and Research, Shirpur 425 405, Maharashtra, India.
Chem Pharm Bull (Tokyo). 2010 Sep;58(9):1168-75. doi: 10.1248/cpb.58.1168.
The aim of the present study was to prepare mucoadhesive multiparticulate system for oral drug delivery using ionic gelation technique. Microspheres of different mucoadhesive polymers including hydroxypropyl methylcellulose (HPMC) K15M and carbopol 971P were prepared. In this technique cross linking of sodium alginate with calcium chloride was done which retarded the release of drug from the mucoadhesive polymer. In the present work atenolol was used as model drug. Interaction studies performed using FT-IR spectroscopy revealed that there was no drug to polymer interactions. Multiparticulates so prepared were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 23-74%. Particle size of the multiparticulates as determined by the scanning electron microscopic analysis (SEM) studies was found to be between 561-831 microm. The prepared formulations also exhibited a good mucoadhesive strength which was determined in in vitro conditions through falling film technique. The multiparticulate so prepared also exhibited a good swelling index which confirmed the strong mucoadhesive property of the formulation. Atenolol release from the multiparticulate system was regulated and extended until 12 h and exhibited a non-Fickian anomalous transport from the swellable microspheres, as evident from the release rate exponent values which varied between 0.569-0.622. The stability studies performed on the optimized batch at 40 degrees C/75% RH for 90 d indicated no significant change in the physicochemical properties. In vivo radioimaging studies in rabbits showed the residence of mucoadhesive microspheres for 6-8 h in upper part of gastrointestinal tract (GIT).
本研究的目的是采用离子凝胶化技术制备用于口服给药的粘膜粘附性多颗粒系统。制备了不同粘膜粘附性聚合物的微球，包括羟丙基甲基纤维素（HPMC）K15M和卡波姆971P。在该技术中，海藻酸钠与氯化钙进行交联，这延缓了药物从粘膜粘附性聚合物中的释放。在本研究中，阿替洛尔用作模型药物。使用傅里叶变换红外光谱进行的相互作用研究表明，药物与聚合物之间没有相互作用。如此制备的多颗粒是离散的、体积大的、自由流动的，平均包封率在23%-74%之间。通过扫描电子显微镜分析（SEM）研究确定的多颗粒粒径在561-831微米之间。所制备的制剂还表现出良好的粘膜粘附强度，这是通过落膜技术在体外条件下测定的。如此制备的多颗粒还表现出良好的溶胀指数，这证实了制剂的强粘膜粘附性能。阿替洛尔从多颗粒系统中的释放得到调节并延长至12小时，并且从可溶胀微球中表现出非菲克反常转运，从释放速率指数值在0.569-0.622之间变化可以明显看出。在40℃/75%相对湿度下对优化批次进行90天的稳定性研究表明，其物理化学性质没有显著变化。在兔子身上进行的体内放射性成像研究表明，粘膜粘附性微球在胃肠道（GIT）上部停留6-8小时。
