Programa de Pós-Graduação em Ciências Farmacêuticas, Curso de Farmácia, Universidade Federal de Santa Maria, Santa Maria, Brazil.
J Control Release. 2011 Jun 30;152(3):370-5. doi: 10.1016/j.jconrel.2011.02.030. Epub 2011 Mar 15.
Spray-dried powders for lung delivery of sodium alendronate (SA) were prepared from hydroalcoholic solutions. Formulations display geometric particle size below to 12 μm and spherical shape associated to a hollow structure. The addition of leucine and ammonium bicarbonate leads to porous particles with rough surfaces. The tapped density ranges from 0.016 to 0.062 g/cm(3), decreasing with the increase of the leucine concentration. For all formulations, the calculated aerodynamic diameters are lower than 5 μm. The in vitro aerodynamic evaluation shows that all powders present a high emitted fraction of 100%, a fine particle fraction ranging from 34.4% to 62.0% and an alveolar fraction ranging from to 23.7% to 42.6%. An optimized sample was evaluated regarding sodium alendronate acute pulmonary toxicity and lung bioavailability. The bronchoalveolar lavage study shows that the intratracheal administration of sodium alendronate dry powder and sodium alendronate aqueous solution do not induce significant increases of lung toxicity indicators as compared with the positive control. Moreover, the intratracheal administration of sodium alendronate dry powder results in a 6.23 ± 0.83% bioavailability, a 3.5-fold increase as compared to oral bioavailability. Finally, these results suggest that sodium alendronate pulmonary delivery could be a new and promising administration route.
用于肺部传递阿仑膦酸钠（SA）的喷雾干燥粉末是由水醇溶液制备的。制剂显示出低于 12μm 的几何粒径和与中空结构相关的球形。亮氨酸和碳酸氢铵的添加导致具有粗糙表面的多孔颗粒。振实密度范围为 0.016 至 0.062g/cm³，随着亮氨酸浓度的增加而降低。对于所有制剂，计算出的空气动力学直径均低于 5μm。体外空气动力学评估表明，所有粉末均具有 100%的高发射分数，细颗粒分数在 34.4%至 62.0%之间，肺泡分数在 23.7%至 42.6%之间。对优化的样品进行了阿仑膦酸钠急性肺毒性和肺部生物利用度评估。支气管肺泡灌洗研究表明，与阳性对照相比，气管内给予阿仑膦酸钠干粉和阿仑膦酸钠水溶液不会引起肺毒性指标的显著增加。此外，气管内给予阿仑膦酸钠干粉可使生物利用度达到 6.23±0.83%，比口服生物利用度增加了 3.5 倍。最后，这些结果表明，肺部传递阿仑膦酸钠可能是一种新的有前途的给药途径。
