Formulation and evaluation of orally disintegrating clopidogrel tablets

ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs) that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC). DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.

摘要 药物递送系统领域的近期研究进展，均致力于提升患者用药依从性。其中一项核心进展为口腔速溶片（orally disintegrating tablets, ODTs）的研发，该剂型可瞬时溶解，无需饮水即可在数秒内释放药物。本研究的核心目标为制备并开发氯吡格雷口腔速溶片。本次研究采用直接压片法制备该口腔速溶片，考察了3种超级崩解剂——交联聚维酮、交联羧甲基纤维素钠、羧甲淀粉钠——分别在3种不同崩解时限条件下对药物溶出速率的影响。对制备得到的片剂进行了硬度、脆碎度、崩解时限以及体外药物释放的评价。此外，本研究采用差示扫描量热法（differential scanning calorimetry, DSC）考察了氯吡格雷与制剂辅料之间的相互作用。差示扫描量热分析结果显示，氯吡格雷与所用辅料之间未发生相互作用。所有片剂的硬度均处于4.0~5.2 kp区间，脆碎度低于1%。所有制剂的重量与药物含量均匀度均符合英国药典（British Pharmacopoeia, BP）规定的官方限度要求。体外药物释放实验结果显示，该口腔速溶片可在10分钟内释放90%以上的药物。人体志愿者适口性评价实验结果表明，该制剂的味觉与口腔触感均符合可接受标准。综上，本次研究所得结果充分证明，所制备的片剂可实现快速崩解，且适口性良好。