Faculty of Chemical and Process Engineering, Warsaw University of Technology, 1 Waryńskiego Street, 00-645 Warsaw, Poland.
Int J Pharm. 2012 Aug 20;433(1-2):51-9. doi: 10.1016/j.ijpharm.2012.04.067. Epub 2012 May 1.
The effectiveness of aerosol therapy is significantly reduced by the mucus layer covering the airways of the tracheobronchial tree. According to the present concept, drug particles are delivered to the lung together with the functional carrier particle that facilitates both the drug transport into the lungs and the penetration of deposited particles through the mucus. The approach of manufacturing multi-component powders with mucoactive compounds and anti-asthmatic medicines (DSCG) bound together in a single particle is additionally considered.
Powders were produced with the spray-drying technique from aqueous precursor solutions containing pure low molecular weight dextran, pure mannitol and dextran/mannitol-N-acetyl cysteine (NAC) mixtures (4:1 and 1:1). NAC has been selected for this purpose as a compound, which is known to be mucolytic. Dextran and mannitol are potentially applicable in the field of inhalation drug delivery. They have been used as stabilizers of functional carrier particles. Powders were characterized for their yield and physicochemical properties including: morphology (SEM), moisture content and thermal properties (DSC). Aerosol performance was determined with NGI impactor after standardized aerosolization of the produced powders in a commercial DPI.
Particle size distributions of dextran-NAC powders were characterized by high fine particle fraction (45-62%), which assures good particle deposition in the lower airways. The thermodynamic properties of the powders based on the temperature of the glass transition T(g) (50-63 °C) suggest the required stability during storage at moderate humidity.
Preliminary examination of the required properties of these particles confirms their potential as functional carriers for pulmonary drug delivery.
气道表面的黏液层会显著降低气溶胶疗法的效果。根据目前的概念，药物颗粒与促进药物向肺部输送和沉积颗粒穿透黏液的功能载体颗粒一起输送到肺部。此外，还考虑了制造多组分粉末的方法，即将具有黏液活性的化合物和抗哮喘药物（DSCG）结合在单个颗粒中的方法。
采用喷雾干燥技术从含有纯低分子量葡聚糖、纯甘露醇和葡聚糖/甘露醇-N-乙酰半胱氨酸（NAC）混合物（4:1 和 1:1）的水前体溶液中制备粉末。选择 NAC 是因为它是一种已知具有黏液溶解作用的化合物。葡聚糖和甘露醇在吸入药物输送领域具有潜在应用。它们被用作功能载体颗粒的稳定剂。粉末的产率和物理化学性质，包括形态（SEM）、水分含量和热性能（DSC）进行了表征。在商业 DPI 中对制备的粉末进行标准化雾化后，使用 NGI 撞击器测定气溶胶性能。
葡聚糖-NAC 粉末的粒径分布特征为高细颗粒分数（45-62%），这确保了在下呼吸道中的良好颗粒沉积。基于玻璃化转变温度 T(g)（50-63°C）的粉末热力学性质表明，在中等湿度下储存时需要稳定性。
对这些颗粒所需特性的初步检查证实了它们作为肺部药物输送的功能载体的潜力。
