Dissolution profile of theophylline modified release tablets, using a biorelevant Dynamic Colon Model (DCM)
Dissolution profile of theophylline modified release tablets, using a biorelevant Dynamic Colon Model (DCM)
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DOI：
10.1016/j.ejpb.2016.08.004
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发表时间：
2016-11-01
影响因子：
4.9
通讯作者：
Simmons, Mark. J. H.
中科院分区：
文献类型：
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作者：
Stamatopoulos, Konstantinos;Batchelor, Hannah K.;Simmons, Mark. J. H.
人类近端结肠被认为是一个有利的网站，以提供药物的局部和全身治疗。然而，修饰的剂型面临复杂且动态变化的结肠环境。因此，已经认识到，除了使用生物相关介质之外，还需要再现流体动力学以创建强大的体外溶出模型，从而能够预测剂型的体内性能。已经开发了一种新的生物相关动态结肠模型（DCM），其提供了平滑肌结构方面的现实环境，在近端人体结肠中发生的物理压力和运动模式。DCM管内部的压力测量证实了压力信号的大小与膜的闭塞率和流体的粘度之间的直接关联。通过在DCM管沿着的不同位置收集样品来评估高度可溶的药物茶碱的溶出曲线和分布。观察到药物释放速率的差异，其受采样点位置、流体粘度和DCM管内混合的影响。使用正电子发射断层扫描获得的DCM管内流体的整体对流运动的图像使示踪剂的分布与茶碱药物的高浓度和低浓度的可能区域的关系成为可能，该信息提供了对药物在剂型通过近端结肠期间可能存在的过饱和和沉淀等广泛现象的更好理解。(C)2016作者由爱思唯尔公司出版
The human proximal colon has been considered a favourable site to deliver drugs for local and systemic treatments. However, modified dosage forms face a complex and dynamically changing colonic environment. Therefore, it has been realized that in addition to the use of biorelevant media, the hydrodynamics also need to be reproduced to create a powerful in vitro dissolution model to enable in vivo performance of the dosage forms to be predicted.A novel biorelevant Dynamic Colon Model (DCM) has been developed which provides a realistic environment in terms of the architecture of the smooth muscle, the physical pressures and the motility patterns occurring in the proximal human colon. Measurements of pressure inside the DCM tube confirmed a direct association between the magnitude of the pressure signal with the occlusion rate of the membrane and the viscosity of the fluid.The dissolution profile and the distribution of the highly soluble drug, theophylline, were assessed by collecting samples at different locations along the DCM tube. Differences in the release rates of the drug were observed which were affected by the sampling point location, the viscosity of the fluid and the mixing within the DCM tube. Images of the overall convective motion of the fluid inside the DCM tube obtained using Positron Emission Tomography enabled relation of the distribution of the tracer to likely areas of high and low concentrations of the theophylline drug.This information provides improved understanding of how extensive phenomena such as supersaturation and precipitation of the drug may be during the passage of the dosage form through the proximal colon. (C) 2016 The Authors. Published by Elsevier B.V.