The Effect of Biorelevant Hydrodynamic Conditions on Drug Dissolution from Extended-Release Tablets in the Dynamic Colon Model.
The Effect of Biorelevant Hydrodynamic Conditions on Drug Dissolution from Extended-Release Tablets in the Dynamic Colon Model.
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DOI：
10.3390/pharmaceutics14102193
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发表时间：
2022-10-14
期刊：
影响因子：
5.4
通讯作者：
Stamatopoulos, Konstantinos
中科院分区：
文献类型：
--
作者：
O'Farrell, Connor;Simmons, Mark J. H.;Batchelor, Hannah K.;Stamatopoulos, Konstantinos
关键词：
在不同的流体动力学条件下，在美国药典（USP）溶出系统II和定制的人结肠体外管状模型，动态结肠模型（DCM）中，研究了茶碱从缓释剂型的体外释放。将从体内数据中提取的五种生物相关运动模式应用于DCM，在基线条件下和使用聚乙二醇或麦芽糖刺激后模拟人近端结肠;这些代表了体内通常预期的运动的下限和上限。在USPII中，在25、50和100 rpm的不同搅拌速度下改变流体动力学条件会影响片剂溶出度。在DCM中应用不同的运动模式影响所产生的溶出曲线，24 h时茶碱释放范围为56.74 ± 2.00%（基线）至96.74 ± 9.63%（麦芽糖刺激）。茶碱的浓度分布显着本地化时，在DCM管的不同部分进行测量，突出了肠模型中的分段管腔的重要性，并在生成空间信息，以支持简单的时间溶解曲线。结果表明，在25 rpm下，未受刺激的健康成人结肠引起的剪切应力可能低于USPII中的剪切应力，因此不足以实现治疗性化合物从羟乙基纤维素基质中的完全释放。当在刺激条件下操作时，DCM中的药物释放在USPII中在25和50 rpm下实现的药物释放之间。
The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII.
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影响因子：
5.4
作者：
Schütt M;O'Farrell C;Stamatopoulos K;Hoad CL;Marciani L;Sulaiman S;Simmons MJH;Batchelor HK;Alexiadis A
通讯作者：
Alexiadis A
影响因子：
3.7
作者：
Maurer, Jacoba M.;Schellekens, Reinout C. A.;Kosterink, Jos G. W.
通讯作者：
Kosterink, Jos G. W.
DOI：
10.1016/j.ejpb.2016.08.004
发表时间：
2016-11-01
影响因子：
4.9
作者：
Stamatopoulos, Konstantinos;Batchelor, Hannah K.;Simmons, Mark. J. H.
通讯作者：
Simmons, Mark. J. H.
影响因子：
5.4
作者：
O'Farrell C;Hoad CL;Stamatopoulos K;Marciani L;Sulaiman S;Simmons MJH;Batchelor HK
通讯作者：
Batchelor HK
影响因子：
24.5
作者：
NARDUCCI, F;BASSOTTI, G;MORELLI, A
通讯作者：
MORELLI, A