Abstract

The aim of this work was to study the effect of gas microbubbles on the production of particles suitable for inhalatory administration by a spray drying technology. An antiasthmatic model drug (sodium cromoglycate) was selected in order to evaluate the effect of different gases (air, CO₂ and N₂) and spray drying operating conditions on the particles aerosolization performance. To this end, gas supersaturated aqueous drug solutions were obtained in a pressurized vessel and then processed by spray drying. The process yield, morphology, size, bulk and tap densities, moisture content and aerosolization properties of the particles were evaluated. The presence of microbubbles in the spray drying feed led to powders with smaller mean geometric sizes than particles obtained without bubbles. The gas-water solubility emerged as a key parameter to obtain inhalatory particles with good aerosolization properties. High water-soluble gases led to bigger particles, while low soluble ones allow to produce smaller particles. The use of air (with an intermediate water solubility respect to CO₂ and N₂) and an adequate set of spray drying operating conditions allowed to obtain sodium cromoglycate particles with superior aerosolization properties than a commercial formulation. Overall, a novel, simple and low-cost method to produce inhalatory particles with excellent aerosolization properties was developed by supersaturating the spray drying liquid feed without using pore-forming agents during the production step, or carriers in the final formulation.

摘要

这项工作的目的是研究气体微泡对通过喷雾干燥技术产生适合吸入给药的颗粒的影响。_{为了评估不同气体（空气、CO 2}和 N ₂）和喷雾干燥操作条件对颗粒雾化性能的影响，选择了一种抗哮喘模型药物（色甘酸钠） 。为此，在加压容器中获得气体过饱和水性药物溶液，然后通过喷雾干燥处理。评价了颗粒的工艺产量、形态、尺寸、堆积密度和振实密度、水分含量和雾化性质。喷雾干燥进料中微气泡的存在导致粉末的平均几何尺寸小于没有气泡的颗粒。气水溶解度成为获得具有良好雾化性能的吸入颗粒的关键参数。高水溶性气体会产生较大的颗粒，而低水溶性气体会产生较小的颗粒。_{使用空气（相对于 CO 2}和 N ₂具有中等水溶性) 和一组适当的喷雾干燥操作条件允许获得具有比商业制剂更优异的气雾化性能的色甘酸钠颗粒。总体而言，通过在生产步骤中不使用造孔剂或最终制剂中的载体，使喷雾干燥液体进料过饱和，开发了一种新型、简单且低成本的方法来生产具有优异雾化性能的吸入性颗粒。