Kim Hyeongmin, Lee Chung-Lyol, Lee Seohyun, Lee Tae Jin, Haleem Iqra, Lee Younghong, Hwang Na Jung, Shim Kyusun, Kim Dohyun, Lee Jaehwi
College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.
Pharmaceutics. 2019 Jun 10;11(6):271. doi: 10.3390/pharmaceutics11060271.
In this study, we aimed to design a highly swellable and mechanically robust matrix tablet (SMT) as a gastroretentive drug-delivery system (GRDDS) capable of improving the dissolution behavior of β-lapachone with low aqueous solubility. For the preparation of SMTs, the cogrinding technique and freeze-thaw method were used to disperse β-lapachone in SMTs in an amorphous state and to enhance the swelling and mechanical properties of SMTs, respectively. As a result, the crystallinity of coground β-lapachone incorporated in the SMTs was found to be considerably decreased; thereby, the dissolution rates of the drug in a simulated gastric fluid could be substantially increased. The SMTs of β-lapachone also demonstrated significantly enhanced swelling and mechanical properties compared to those of a marketed product. The reason for this might be because the physically crosslinked polymeric networks with a porous structure that were formed in SMTs through the freeze-thaw method. In addition, β-lapachone was gradually released from the SMTs in 6 h. Therefore, SMTs of β-lapachone developed in this study could be used as GRDDS with appropriate swelling and mechanical properties for improving the dissolution behavior of hydrophobic drugs such as β-lapachone.
在本研究中，我们旨在设计一种具有高膨胀性和机械强度的骨架片（SMT）作为胃滞留给药系统（GRDDS），以改善低水溶性β-拉帕醌的溶出行为。对于SMT的制备，采用共研磨技术和冻融法分别将β-拉帕醌以无定形状态分散在SMT中，并增强SMT的膨胀和机械性能。结果发现，掺入SMT中的共研磨β-拉帕醌的结晶度显著降低；因此，药物在模拟胃液中的溶出速率可大幅提高。与市售产品相比，β-拉帕醌的SMT还表现出显著增强的膨胀和机械性能。其原因可能是通过冻融法在SMT中形成了具有多孔结构的物理交联聚合物网络。此外，β-拉帕醌在6小时内从SMT中逐渐释放。因此，本研究中开发的β-拉帕醌SMT可作为具有适当膨胀和机械性能的GRDDS，用于改善疏水性药物如β-拉帕醌的溶出行为。
