Perioli Luana, Ambrogi Valeria, Giovagnoli Stefano, Blasi Paolo, Mancini Alessandra, Ricci Maurizio, Rossi Carlo
Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo, 1, Perugia 06123, Italy.
AAPS PharmSciTech. 2008;9(1):274-81. doi: 10.1208/s12249-007-9029-1. Epub 2008 Jan 17.
The purpose of this research was to study the compression force influence on polymers, tablet behavior and drug release rate. Several tablet batches were produced by varying the compression force and by using hydroxyethyl cellulose (HEC) and Carbopol 940 in the 1:1 ratio as matrix forming polymers. All batches were characterized by DSC and X-ray analyses and in terms of swelling, ex vivo and in vivo mucoadhesive time, ex vivo mucoadhesion force, and in vitro and in vivo release. No significant excipient-excipient or excipient-drug interactions were observed in any of the batches. All the tablets hydrated quickly and their high hydration percentage showed that the compression forces used did not remarkably affect the water penetration and the polymeric chain stretching. Mucoadhesion performances and drug release were mainly influenced by compression force; its increase produced higher ex vivo and in vivo mucoadhesion and the in vitro and in vivo drug releases were seen to decrease with the increase of the compression force. However tablets fabricated by using the lowest compression force showed the best in vivo mucoadhesive time and hydrated faster when compared to the others. Tablets 4 and 5, prepared with the highest forces, caused pain during in vivo application and gave rise to irritation needing to be detached by the volunteers while tablet 1, prepared with the lowest force, gave the best results because it was able to produce the highest drug salivary concentration and no pain. All tablets exhibited an anomalous release mechanism.
本研究的目的是研究压缩力对聚合物、片剂行为和药物释放速率的影响。通过改变压缩力，并以1:1的比例使用羟乙基纤维素（HEC）和卡波姆940作为基质形成聚合物，制备了几个片剂批次。所有批次均通过差示扫描量热法（DSC）和X射线分析进行表征，并对其溶胀、体外和体内粘膜粘附时间、体外粘膜粘附力以及体外和体内释放进行了研究。在任何批次中均未观察到明显的辅料-辅料或辅料-药物相互作用。所有片剂均能快速水化，其高水化率表明所使用的压缩力对水渗透和聚合物链拉伸没有显著影响。粘膜粘附性能和药物释放主要受压缩力影响；压缩力增加会产生更高的体外和体内粘膜粘附力，并且体外和体内药物释放随压缩力增加而降低。然而，使用最低压缩力制备的片剂显示出最佳的体内粘膜粘附时间，并且与其他片剂相比水化更快。用最高压力制备的片剂4和片剂5在体内应用时引起疼痛，并导致志愿者出现刺激反应，需要将其取下，而用最低压力制备的片剂1则取得了最佳效果，因为它能够产生最高的药物唾液浓度且无疼痛。所有片剂均表现出非正规的释放机制。
