Varshosaz Jaleh, Taymouri Somayeh, Hamishehkar Hamed, Vatankhah Razieh, Yaghubi Shadi
Department of Pharmaceutics and Novel Drug Delivery Systems Research Centre, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, I.R. Iran.
Res Pharm Sci. 2017 Jun;12(3):222-232. doi: 10.4103/1735-5362.207203.
Inhalable dry powders containing poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were developed for the delivery of tadalafil (TAD) for treatment of life-treating pulmonary arterial hypertension. Taguchi design was employed to evaluate the effects of different formulation variables on the physicochemical characteristics of PLGA-NPs prepared using emulsion solvent evaporation method. Inhalable PLGA-NPs of TAD were successfully prepared by co-spray drying the PLGA-NPs with inert carriers. Physicochemical characteristics and deposition of the aerosolized drug were also evaluated. The optimized formulation was prepared using 7.5 mg of PLGA, 2.5 mg of TAD, sonication time of 6 min and 2% polyvinyl alcohol (PVA) as the stabilizer. The optimized aqueous/oil phase ratio for PLGA-NPs preparation was 10:1. Polymer/drug ratio was the most effective parameter on the release efficiency. Encapsulation efficiency, zeta potential and particle size of PLGA-NPs were more affected by aqueous/organic phase ratio. The spray dried powders containing PLGA-NPs had a mass median aerodynamic diameter (MMAD) in the range of 1.4-2.8 μm that was suitable for TAD delivery to the deep region of lung. The presence of L- leucine in mannitol containing formulations decreased the interparticulate forces between particles and increased significantly the process yield and fine particle fraction (FPF). The results indicated that prepared dry powders containing TAD-loaded PLGA-NPs were suitable for inhalation and has the potential for the treatment of pulmonary arterial hypertension.
开发了含有聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒（NPs）的可吸入干粉，用于递送他达拉非（TAD）以治疗危及生命的肺动脉高压。采用田口设计来评估不同配方变量对使用乳液溶剂蒸发法制备的PLGA-NPs理化特性的影响。通过将PLGA-NPs与惰性载体共喷雾干燥，成功制备了可吸入的TAD-PLGA-NPs。还评估了雾化药物的理化特性和沉积情况。使用7.5mg的PLGA、2.5mg的TAD、6分钟的超声处理时间和2%的聚乙烯醇（PVA）作为稳定剂制备了优化配方。制备PLGA-NPs的最佳水/油相比为10:1。聚合物/药物比是对释放效率影响最显著的参数。PLGA-NPs的包封率、zeta电位和粒径受水/有机相比的影响更大。含有PLGA-NPs的喷雾干燥粉末的质量中值空气动力学直径（MMAD）在1.4-2.8μm范围内，适合将TAD递送至肺部深部区域。含甘露醇配方中L-亮氨酸的存在降低了颗粒间的作用力，并显著提高了工艺产率和细颗粒分数（FPF）。结果表明，制备的含有载TAD的PLGA-NPs的干粉适合吸入，具有治疗肺动脉高压的潜力。
