Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Physical Pharmaceutics, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
J Pharm Sci. 2018 Jul;107(7):1896-1902. doi: 10.1016/j.xphs.2018.02.022. Epub 2018 Mar 14.
First, an elementary osmotic pump (EOP) with a simple structure was prepared using polyethylene oxide (PEO) and NaCl as an excipient, and the influence of the molecular weight (Mw) of PEO on drug release was investigated. In the dissolution test of EOP, it was observed that the gelated core tablet was pushed out through the orifice. The dissolution profile of EOP was sigmoidal, and despite the short time, a zero-order release region was observed. The gel swelling rate in the zero-order region was independent of the Mw of PEO. It was also found that higher the Mw of PEO, the larger the saturated swelling amount. Next, a push-pull pump (PPP) with almost identical formulation to that of EOP was prepared, and its drug release characteristics were investigated. PPPs were prepared by varying the combination of Mws of PEO in both layers, and their dissolution profiles were compared. It was found that PPP using a low-Mw PEO for the drug layer and PEO with a high-Mw in the push layer showed the longest dissolution profile of the linear region. The obtained findings suggested that the properties of PEO and its hydrogel play a crucial role in the drug release of PPP.
首先,使用聚乙烯氧化物 (PEO) 和 NaCl 作为赋形剂制备了一种结构简单的基本渗透泵 (EOP),并研究了 PEO 的分子量 (Mw) 对药物释放的影响。在 EOP 的溶解试验中,观察到凝胶化的核心片剂通过孔口被推出。EOP 的溶解曲线呈 S 形,尽管时间很短,但观察到零级释放区域。零级区域中凝胶的溶胀速率与 PEO 的 Mw 无关。还发现,PEO 的 Mw 越高,饱和溶胀量越大。接下来,制备了与 EOP 几乎相同配方的推拉泵 (PPP),并研究了其药物释放特性。通过改变两层 PEO 的 Mw 的组合来制备 PPP,并比较它们的溶解曲线。结果发现,药物层使用低 Mw PEO 而推动层使用高 Mw PEO 的 PPP 显示出最长的线性区域溶解曲线。研究结果表明,PEO 及其水凝胶的性质在 PPP 的药物释放中起着至关重要的作用。