University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic; Zentiva, k.s., U Kabelovny 130, 102 00 Prague 10, Czech Republic.
Zentiva, k.s., U Kabelovny 130, 102 00 Prague 10, Czech Republic.
Int J Pharm. 2020 Sep 25;587:119719. doi: 10.1016/j.ijpharm.2020.119719. Epub 2020 Jul 31.
Efficient tablet disintegration is a pre-requisite for fast and complete drug dissolution from immediate release formulations. While the overall tablet disintegration time is a routinely measured quality attribute of pharmaceutical products, little attention is usually paid to the analysis of disintegration fragments and the cascade of elementary steps that lead to their formation. In this work, we investigate the disintegration pathways of directly compressed tablets by a unique combination of three methods: (i) magnetic resonance imaging (MRI), to gain insight into structural changes of tablets during disintegration; (ii) texture analysis, to measure the disintegration kinetics; and (iii) static light scattering, to characterise the size distribution of disintegration fragments. By systematically varying the tablet composition (50-90% of ibuprofen as a model active ingredient, 0-4% of croscarmellose sodium disintegrant, 6-50% of lactose monohydrate filler), a relationship between the tablet formulation, the size distribution of the disintegration fragments and the dissolution rate of the active ingredient has been established. To interpret the experimental observations, we analyse the disintegration fragments by Raman mapping and relate their composition and structure to the micro-scale arrangement of individual formulation components inside the tablet.
片剂的高效崩解是速释制剂中药物快速完全溶出的前提条件。虽然整体片剂崩解时间是药品的常规质量属性，但通常很少关注崩解碎片的分析以及导致其形成的基本步骤的级联。在这项工作中，我们通过三种方法的独特组合研究了直接压片的崩解途径：(i)磁共振成像 (MRI)，以深入了解崩解过程中片剂的结构变化；(ii) 纹理分析，测量崩解动力学；和 (iii) 静态光散射，以表征崩解碎片的尺寸分布。通过系统地改变片剂组成（布洛芬作为模型活性成分的 50-90%、崩解剂羧甲纤维素钠的 0-4%、填充剂一水乳糖的 6-50%），建立了片剂配方、崩解碎片的尺寸分布和活性成分溶出率之间的关系。为了解释实验观察结果，我们通过拉曼映射分析崩解碎片，并将它们的组成和结构与片剂内部各个配方成分的微观排列相关联。
