SSPC Pharmaceutical Research Centre, School of Pharmacy, University College Cork, Cork, Ireland.
SSPC Pharmaceutical Research Centre, School of Chemical and Bioprocess Engineering, University College Dublin, Dublin 4, Ireland; APC Ltd, Cherrywood Business Park, Loughlinstown, Co Dublin, Ireland.
Int J Pharm. 2020 Nov 15;589:119838. doi: 10.1016/j.ijpharm.2020.119838. Epub 2020 Sep 3.
The study presented was conducted to determine whether a percolation threshold value, previously determined for ibuprofen/microcrystalline cellulose (MCC) blends using percolation theory and compression data (Queiroz et al., 2019), could translate to tablet disintegration and dissolution data. The influence of MCC grade (air stream dried versus spray dried) on tablet disintegration and dissolution was also investigated. Complementary to conventional disintegration and dissolution testing, Raman imaging determined drug distribution within tablets, and in-line particle video microscopy (PVM) and focused-beam reflectance measurement (FBRM) monitored tablet disintegration. Tablets were prepared containing 0-30% w/w ibuprofen. Raman imaging confirmed the percolation threshold by quantifying the number and equivalent circular diameters of ibuprofen domains on tablet surfaces. Across the percolation threshold, a step change in dissolution behaviour occurred, and tablets containing air stream dried MCC showed slower disintegration rates compared to tablets containing spray dried MCC. Dissolution measurements confirmed experimentally a percolation threshold in agreement with that determined using percolation theory and compression data. An increase in drug domains, due to cluster formation, and less efficient tablet disintegration contributed to slower ibuprofen dissolution above the percolation threshold. Slower dissolution was measured for tablets containing air stream dried compared to spray dried MCC.
本研究旨在确定先前使用渗透理论和压缩数据（Queiroz 等人，2019）确定的布洛芬/微晶纤维素（MCC）混合物的渗透阈值是否可以转化为片剂崩解和溶解数据。还研究了 MCC 等级（气流干燥与喷雾干燥）对片剂崩解和溶解的影响。除了常规的崩解和溶解测试外，拉曼成像还确定了药物在片剂中的分布，在线粒子视频显微镜（PVM）和聚焦光束反射测量（FBRM）监测片剂崩解。制备了含有 0-30%w/w 布洛芬的片剂。拉曼成像通过定量片剂表面布洛芬域的数量和等效圆直径来证实了渗透阈值。在渗透阈值处，溶解行为发生了阶跃变化，并且含有气流干燥 MCC 的片剂的崩解速率比含有喷雾干燥 MCC 的片剂慢。溶解测量结果证实了实验中存在与使用渗透理论和压缩数据确定的渗透阈值一致的渗透阈值。由于簇形成导致药物域增加，以及片剂崩解效率降低，导致渗透阈值以上布洛芬的溶解速度减慢。与喷雾干燥 MCC 相比，气流干燥 MCC 含量较高的片剂溶解速度较慢。
