Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province, 110016, China.
AAPS PharmSciTech. 2018 Feb;19(2):610-620. doi: 10.1208/s12249-017-0873-3. Epub 2017 Sep 15.
The objective of this study was to prepare time-controlled release etodolac pellets to facilitate drug administration according to the body's biological rhythm, optimize the drug's desired effects, and minimize adverse effects. The preparation consisted of three laminal layers from center to outside: the core, the swelling layer, and the insoluble polymer membrane. Factors influenced the core and the coating films were investigated in this study. The core pellets formulated with etodolac, lactose, and sodium carboxymethyl starch (CMS-Na) were prepared by extrusion-spheronization and then coated by a fluidized bed coater. Croscarmellose sodium (CC-Na) was selected as the swelling agent, and ethyl cellulose (EC) as the controlled release layer. The prepared pellets were characterized by scanning electron microscopy and evaluated by a dissolution test and a pharmacokinetic study. Compared with commercial available capsules, pharmacokinetics studies in beagle dogs indicated that the prepared pellets release the drug within a short period of time, immediately after a predetermined lag time. A good correlation between in vitro dissolution and in vivo absorption of the pellets was exhibited in the analysis.
本研究的目的是制备时控释放依托度酸微丸，以便根据人体的生物节律给药，优化药物的预期效果，并最小化不良反应。该制剂由从内到外的三个层组成：核心、膨胀层和不溶性聚合物膜。本研究考察了影响核心和包衣膜的因素。采用挤出滚圆法制备以依托度酸、乳糖和羧甲基淀粉钠（CMS-Na）为核心的微丸，然后用流化床包衣机进行包衣。交联羧甲基纤维素钠（CC-Na）被选为膨胀剂，乙基纤维素（EC）作为控释层。通过扫描电子显微镜对制备的微丸进行了表征，并通过溶出度试验和药代动力学研究进行了评价。与市售胶囊相比，在比格犬中的药代动力学研究表明，制备的微丸在预定的滞后时间后，在短时间内迅速释放药物。在分析中显示出微丸的体外溶出度与体内吸收之间具有良好的相关性。
