Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan.
Int J Pharm. 2011 Apr 15;408(1-2):84-90. doi: 10.1016/j.ijpharm.2011.01.053. Epub 2011 Feb 1.
The objective of the present study was to determine the optimum composition for sustained-release of tamsulosin hydrochloride from microparticles intended for orally disintegrating tablets. Microparticles were prepared from an aqueous ethylcellulose dispersion (Aquacoa®), and an aqueous copolymer based on ethyl acrylate and methyl methacrylate dispersion (Eudragit®) NE30D), with microcrystalline cellulose as core particles with a fluidized bed coating process. Prepared microparticles were about 200 μm diameter and spherical. The microparticles were evaluated for in vitro drug release and in vivo absorption to assess bioequivalence in a commercial product, Harnal® pellets. The optimum ratio of Aquacoat® and Eudragit® NE30D in the matrix was 9:1. We observed similar drug release profiles in microparticles and Harnal® pellets. Higuchi model analysis of the in vitro drug release from microparticles was linear up to 80% release, typical of Fickian diffusion sustained-release profile. The in vivo absorption properties from microparticles were comparable to Harnal® pellets, and there was a linear relationship between in vitro drug release and in vivo drug release. In conclusion, this development produces microparticles in single-step coating, that provided a sustained-release of tamsulosin hydrochloride comparable to Harnal® pellets.
本研究旨在确定盐酸坦索罗辛从用于口腔崩解片的微丸中持续释放的最佳配方。微丸由水性乙基纤维素分散体（Aquacoa®）和基于丙烯酸乙酯和甲基丙烯酸甲酯的水性共聚物分散体（Eudragit® NE30D）以及微晶纤维素作为核心颗粒的流化床包衣工艺制备。制备的微丸直径约为 200μm，呈球形。通过体外药物释放和体内吸收评估微丸，以评估商业产品 Harnal®丸剂的生物等效性。基质中 Aquacoat®和 Eudragit® NE30D 的最佳比例为 9:1。我们观察到微丸和 Harnal®丸剂具有相似的药物释放曲线。微丸体外药物释放的 Higuchi 模型分析在 80%释放之前呈线性，典型的为菲克扩散持续释放曲线。从微丸中体内吸收特性与 Harnal®丸剂相当，体外药物释放与体内药物释放之间存在线性关系。总之，该方法可一步法包衣制备微丸，提供与 Harnal®丸剂相当的盐酸坦索罗辛持续释放。
