Randale Shivsagar Ashok, Dabhi Chandu Somatbhai, Tekade Avinash Ramrao, Belgamwar Veena Shailendra, Gattani Surendra Ganeshlal, Surana Sanjay Javarilal
Department of Pharmaceutics, R C Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
Chem Pharm Bull (Tokyo). 2010 Apr;58(4):443-8. doi: 10.1248/cpb.58.443.
The purpose of this study was to mask the intensely bitter taste of metoclopramide HCl and to formulate a rapid disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing metoclopramide HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratio by the extrusion-precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.8, taste evaluation in oral cavity and molecular property. The complex having drug-polymer ratio of 1 : 2 shows significant taste masking, confirmed by drug release in SSF and in-vivo taste evaluation; therefore, it was selected for further study. Taste evaluation of DPCs in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) within 10 s, whereas, metoclopramide HCl was rated intensely bitter with a score of +3 for 10 s. Tablets were evaluated for various parameters like tensile strength, wetting time, water absorption ratio, in-vitro disintegration time, and disintegration in oral cavity. The effect of diluents, lubricants and sweetening agent (Xylisorb) on the disintegration time was also evaluated. Tablets of batch F3 containing mannitol and microcrystalline cellulose in the ratio 1 : 1 and 8% w/w crosspovidone showed faster disintegration (within 20 s) than the marketed formulation (180 s). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Tablets of batch F3 also revealed rapid drug release (t(90), 90 s) in SGF compared with marketed formulation (t(90), 600 s).
本研究的目的是掩盖盐酸甲氧氯普胺的强烈苦味，并制备该掩味药物的快速崩解片（RDT）。通过挤压沉淀法将盐酸甲氧氯普胺与甲基丙烯酸氨基烷基酯共聚物（Eudragit EPO）以不同比例络合来实现掩味。对药物 - 聚合物复合物（DPCs）进行了药物含量、pH 6.8模拟唾液（SSF）中的体外味觉、口腔味觉评价和分子性质测试。药物与聚合物比例为1:2的复合物显示出显著的掩味效果，这通过在SSF中的药物释放和体内味觉评价得到证实；因此，选择该复合物进行进一步研究。在人类志愿者中对DPCs进行的味觉评价显示，在10秒内苦味程度低于阈值（0.5），具有相当程度的掩味效果，而盐酸甲氧氯普胺在10秒内被评为强烈苦味，评分为 +3。对片剂进行了各种参数评估，如拉伸强度、润湿时间、吸水率、体外崩解时间和口腔崩解情况。还评估了稀释剂、润滑剂和甜味剂（Xylisorb）对崩解时间的影响。含有比例为1:1的甘露醇和微晶纤维素以及8% w/w交联聚维酮的F3批次片剂显示出比市售制剂（180秒）更快的崩解速度（在20秒内）。体外崩解行为与口腔崩解情况之间具有良好的相关性。与市售制剂（t(90)，600秒）相比，F3批次片剂在模拟胃液（SGF）中也显示出快速的药物释放（t(90)，90秒）。
