Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7362, USA.
Carbohydr Polym. 2013 Feb 15;92(2):1915-20. doi: 10.1016/j.carbpol.2012.11.071. Epub 2012 Nov 30.
A penta-ethyl ester prodrug of the radionuclide decorporation agent diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was encapsulated in alginate beads by the ionotropic gelation method. An optimal formulation was found by varying initial concentrations of DTPA penta-ethyl ester, alginate polymer, Tween 80 surfactant and calcium chloride. All prepared alginate beads were ~1.6mm in diameter, and the optimal formulation had loading and encapsulation efficiencies of 91.0±1.1 and 72.6±2.2%, respectively, and only 3.2±0.8% water absorption after storage at room temperature in ~80% relative humidity. Moreover, Fourier transform infrared spectroscopy showed that DTPA penta-ethyl ester did not react with excipients during formation of the DTPA penta-ethyl ester-containing alginate beads. Release of prodrug from alginate beads was via anomalous transport, and its stability enhanced by encapsulation. Collectively, these data suggest that this solid dosage form may be suitable for oral administration after radionuclide contamination.
放射性核素解毒剂二乙烯三胺五乙酸(DTPA)的五乙酯前药是一种油性液体,采用离子凝胶法包封在海藻酸盐珠中。通过改变 DTPA 五乙酯、海藻酸盐聚合物、吐温 80 表面活性剂和氯化钙的初始浓度,找到了最佳配方。所有制备的海藻酸盐珠的直径约为 1.6mm,最佳配方的载药量和包封率分别为 91.0±1.1%和 72.6±2.2%,在相对湿度约为 80%的室温下储存 3.2±0.8%的吸水率。此外,傅里叶变换红外光谱表明,DTPA 五乙酯在形成含 DTPA 五乙酯的海藻酸盐珠时没有与赋形剂发生反应。前药从海藻酸盐珠中的释放是通过异常转运,其稳定性通过包封得到增强。总的来说,这些数据表明,这种固体剂型在放射性核素污染后可能适合口服。