Department of Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 17, 44121 Ferrara, Italy.
J Microencapsul. 2012;29(3):225-33. doi: 10.3109/02652048.2011.646326. Epub 2011 Dec 30.
The aim of this study was to prepare lipid microparticles (LMs) loaded with the polar bronchodilator agent salbutamol, and designed for sustained release pulmonary delivery. The microparticles were produced by melt emulsification followed by a sonication step, using different biocompatible lipid carriers (tristearin, stearic acid and glyceryl behenate) and phosphatidylcholine as the surfactant. The use of salbutamol free base, rather than salbutamol sulphate, was necessary to obtain the incorporation of the drug in the lipid particle matrix. The prolonged release of salbutamol base was achieved only by the glyceryl behenate microparticles (40.9% of encapsulated drug being released after 8 h). The salbutamol loading was 4.2% ± 0.1 and the mass median diameter, determined by laser diffraction, ranged from 4.8 to 5.4 µm. The sustained release of LMs were formulated as a carrier-free dry powder for inhalation and exhibited a fine particle fraction of 17.3% ± 2.2, as measured by multi-stage liquid impinger.
本研究旨在制备负载极性支气管扩张剂沙丁胺醇的脂质微粒（LMs），并设计用于持续释放肺部给药。通过熔融乳化，随后进行超声处理，使用不同的生物相容性脂质载体（三硬脂精、硬脂酸和甘油山嵛酸酯）和磷脂作为表面活性剂，制备了微球。使用沙丁胺醇游离碱而不是硫酸沙丁胺醇，是为了将药物掺入脂质颗粒基质中。只有甘油山嵛酸酯微球才能实现沙丁胺醇游离碱的延长释放（8 小时后释放了 40.9%的包裹药物）。沙丁胺醇的载药量为 4.2%±0.1，通过激光衍射法测定的质量中值直径为 4.8 至 5.4 µm。将 LMs 制成无载体干粉吸入剂进行持续释放，通过多级液体撞击器测量，其微细颗粒分数为 17.3%±2.2。
