State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
Int J Pharm. 2012 Oct 15;436(1-2):1-9. doi: 10.1016/j.ijpharm.2012.06.038. Epub 2012 Jun 23.
Beclomethasone dipropionate (BDP), which is a member in the inhaled glucocorticosteroid class, is commonly used in the treatment of asthma by pulmonary delivery. The purpose of this study is to prepare ultrafine BDP particles for dry powder inhalation (DPI) administration by combining microfluidic antisolvent precipitation without surfactant, high-pressure homogenization (HPH) and spray drying. T-junction microchannel was adopted for the preparation of needle-like BDP particles. The needle-like particles could be easily broken down into smaller particles during HPH, which were assembled into uniform low-density spherical BDP aggregates by spray drying. The effects of the operation parameters, such as the flow rates of BDP methanol solution and antisolvent, the overall flow rate, the BDP concentration, and the change of the injection phase on BDP particle size were explored. The results indicated that the BDP particle size greatly decreased with the reduction of BDP solution flow rate and the increase of antisolvent flow rate. However, the BDP particle size firstly decreased and then increased with the increase of the overall flow rate and the increase of BDP concentration. Also, BDP solution as the injection phase could form the smaller BDP particles. 10 HPH cycles are enough to forming short rod-like particles. After spray drying, the BDP spherical aggregates with a 2-3 μm size could be achieved. They have an excellent aerosol performance, 2.8 and 1.4 times as many as raw BDP and vacuum-dried BDP particles, respectively.
倍氯米松二丙酯（BDP）是吸入性糖皮质激素类药物的一种，通常通过肺部给药来治疗哮喘。本研究旨在通过结合无表面活性剂的微流控反溶剂沉淀、高压匀质（HPH）和喷雾干燥来制备用于干粉吸入（DPI）的 BDP 超细颗粒。T 型 Junction 微通道用于制备针状 BDP 颗粒。在 HPH 过程中，针状颗粒很容易被进一步破碎成更小的颗粒，然后通过喷雾干燥组装成均匀的低密度球形 BDP 聚集体。考察了操作参数，如 BDP 甲醇溶液和反溶剂的流速、总流速、BDP 浓度以及注入相的变化对 BDP 粒径的影响。结果表明，BDP 粒径随 BDP 溶液流速的降低和反溶剂流速的增加而显著减小。然而，BDP 粒径先减小后增大，随着总流速和 BDP 浓度的增加而增大。此外，BDP 溶液作为注入相可以形成更小的 BDP 颗粒。10 次 HPH 循环足以形成短棒状颗粒。喷雾干燥后，可得到粒径为 2-3μm 的 BDP 球形聚集体。它们具有优异的气溶胶性能，分别是原始 BDP 颗粒和真空干燥 BDP 颗粒的 2.8 倍和 1.4 倍。
