表面活性剂包结脂溶性药物插层水滑石的制备及药物释放动力学研究
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摘要
本论文利用双滴共沉淀法分别制备了胆酸根包结泼尼松、胆酸根包结炔雌醇、油酸根包结泼尼松和油酸根包结炔雌醇插层水滑石复合材料。采用XRD、FT-IR、UV-vis、荧光分光光度计、元素分析、TG-DTA等测试手段确定其超分子结构和化学组成。研究发现,表面活性剂可包合中性的脂溶性药物分子形成胶束并进入水滑石层间。
模拟人体环境,对三种插层复合物(胆酸根包结泼尼松、胆酸根包结炔雌醇和油酸根包结泼尼松插层水滑)进行了药物体外释放研究。采用DEBS法,以SUM值最小为原则,分别采用四种动力学模型对药物释放动力学进行拟合。通过R-P方程中的参数n值探讨了药物释放机理:高pH值条件下的释放一般由离子交换控制,而低pH值时药物的释放受离子交换和层板溶蚀二者共同作用。
本论文工作探讨了水滑石类层状材料对脂溶性药物的负载和缓释行为,为将该无机层状材料用于药物缓释体系提供了新的研究思路,具有潜在的应用前景。
Four drug-inorganic composites involving hydrophobic drug-surfactant micelles intercalated Mg-Al layered double hydroxide (LDH) have been assembled by coprecipitation method. The selected hydrophobic drugs were prednisone (PNS) and Ethinylestradiol (EE), and sodium cholate (SC) and sodium oleate (SO) were shosen as the surfactants. Powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and UV-vis absorption spectroscopy indicate a successful intercalation of drug-containing micelles into galleries of LDH matrix.
The in vitro drug release studies of three composites (PNS/SC-LDHs, PNS/SO-LDHs and EE/SC-LDHs) were investigated in detail. Four kinetic models (first-order equation, Higuchi equation, Bhaskas equation and Ritger-peppas equation) were chosen respectively to study the release kinetics of hydrophobic drugs from LDH carrier, and it was found that this process can be described satisfactorily by Directing Excel-based Solver (DEBS). The drug release mechanism was discussed by the n value in the R-P equation. The release mechanism is based on drug diffusion at high pH value, while the drug release behavior depends on the combination control of ion-exchange and dissolution of the composite at low pH value. Therefore, it is concluded that the MgAl-LDH can be potentially used as an inorganic drug carrier for hydrophobic drugs in a wide pH circumstance.
模拟人体环境,对三种插层复合物(胆酸根包结泼尼松、胆酸根包结炔雌醇和油酸根包结泼尼松插层水滑)进行了药物体外释放研究。采用DEBS法,以SUM值最小为原则,分别采用四种动力学模型对药物释放动力学进行拟合。通过R-P方程中的参数n值探讨了药物释放机理:高pH值条件下的释放一般由离子交换控制,而低pH值时药物的释放受离子交换和层板溶蚀二者共同作用。
本论文工作探讨了水滑石类层状材料对脂溶性药物的负载和缓释行为,为将该无机层状材料用于药物缓释体系提供了新的研究思路,具有潜在的应用前景。
Four drug-inorganic composites involving hydrophobic drug-surfactant micelles intercalated Mg-Al layered double hydroxide (LDH) have been assembled by coprecipitation method. The selected hydrophobic drugs were prednisone (PNS) and Ethinylestradiol (EE), and sodium cholate (SC) and sodium oleate (SO) were shosen as the surfactants. Powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and UV-vis absorption spectroscopy indicate a successful intercalation of drug-containing micelles into galleries of LDH matrix.
The in vitro drug release studies of three composites (PNS/SC-LDHs, PNS/SO-LDHs and EE/SC-LDHs) were investigated in detail. Four kinetic models (first-order equation, Higuchi equation, Bhaskas equation and Ritger-peppas equation) were chosen respectively to study the release kinetics of hydrophobic drugs from LDH carrier, and it was found that this process can be described satisfactorily by Directing Excel-based Solver (DEBS). The drug release mechanism was discussed by the n value in the R-P equation. The release mechanism is based on drug diffusion at high pH value, while the drug release behavior depends on the combination control of ion-exchange and dissolution of the composite at low pH value. Therefore, it is concluded that the MgAl-LDH can be potentially used as an inorganic drug carrier for hydrophobic drugs in a wide pH circumstance.
引文
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