Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion
Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion
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DOI：
10.1016/j.ijpharm.2003.09.037
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发表时间：
2004-01-28
影响因子：
5.8
通讯作者：
McGinity, JW
中科院分区：
文献类型：
--
作者：
Crowley, MM;Schroeder, B;McGinity, JW
本研究的目的是确定的物理化学性质，并探讨从乙基纤维素（EC）骨架片的药物释放机制，无论是直接压缩或热熔挤出（HME）的二元混合物的水溶性药物（愈创甘油醚）和聚合物。将乙基纤维素分离成分别对应于325-80和80-30目颗粒的“细”或“粗”粒度级分。在10、30或50 kN的压制力下制备含30%愈创甘油醚的片剂，并在80-90和90- 110 ℃的加工温度下挤出。采用氦比重瓶法、压汞法、差示扫描量热法和扫描电子显微镜等方法研究了药物的溶出和释放动力学，并考察了片剂的孔隙特征、弯曲度、热性能和表面形貌。的曲折度直接测量的一种新的技术，允许在三个实验中的扩散系数的计算。应用Higuchi扩散模型、逾渗理论和聚合物自由体积理论解释药物从骨架系统中的释放特性。释放速率取决于乙基纤维素颗粒大小、压制力和挤出温度。(C)2003 Elsevier B. V.保留所有权利。
The objective of this research project was to determine the physicochemical properties and investigate the drug release mechanism from ethyl cellulose (EC) matrix tablets prepared by either direct compression or hot-melt extrusion (HME) of binary mixtures of water soluble drug (guaifenesin) and the polymer. Ethyl cellulose was separated into "fine" or "coarse" particle size fractions corresponding to 325-80 and 80-30 mesh particles, respectively. Tablets containing 30% guaifenesin were prepared at 10, 30, or 50 kN compaction forces and extruded at processing temperatures of 80-90 and 90-110degreesC. The drug dissolution and release kinetics were determined and the tablet pore characteristics, tortuosity, thermal properties and surface morphologies were studied using helium pycnometry, mercury porosimetry, differential scanning calorimetry and scanning electron microscopy. The tortuosity was measured directly by a novel technique that allows for the calculation of diffusion coefficients in three experiments. The Higuchi diffusion model, Percolation Theory and Polymer Free Volume Theory were applied to the dissolution data to explain the release properties of drug from the matrix systems. The release rate was shown to be dependent on the ethyl cellulose particle size, compaction force and extrusion temperature. (C) 2003 Elsevier B.V. All rights reserved.