Ghasemian Elham, Vatanara Alireza, Rouini Mohammad Reza, Rouholamini Najafabadi Abdolhossein, Gilani Kambiz, Lavasani Hoda, Mohajel Nasir
a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
b Department of Virology , Pasteur Institute of Iran , Tehran , Iran.
Pharm Dev Technol. 2016 Dec;21(8):961-971. doi: 10.3109/10837450.2015.1086369. Epub 2015 Oct 1.
Administration of sildenafil citrate (SC) is considered as a strategy in the treatment of pulmonary hypertension.
This study reports production of the inhalable microparticles containing SC-loaded poly(lactide-co-glycolic acid)-nanoparticles.
SC-nanoparticles were prepared by the double emulsion solvent evaporation method. Next, free SC and SC-loaded nanoparticles were spray dried in the presence of appropriate excipients (lactose, maltose and trehalose). Physicochemical properties and aerodynamic behavior of prepared powders were evaluated. In addition, drug accumulation from selected formulations in the rat lung tissue was compared with oral and IV administration.
Size and fine particle fraction of selected nanocomposites and free SC microparticles were 7 and 4.5 µm, and 60.2% and 68.2%, respectively. Following oral and IV administration, the drug was not detectable in the lung after 4 and 6 h, respectively, but in SC-loaded nanoparticles, the drug was detectable in the lung even after 12 h of inhalation. Respirable particles containing free SC provided high concentration at first that was detectable up to 6 after insufflation.
In vivo study demonstrated that pulmonary administration of sildenafil and sildenafil nanoparticles produced longer half-life and higher concentration of the drug in the lung tissue as compared to oral and IV administration. So, these formulations could be more effective than oral and IV administration of this drug.
枸橼酸西地那非（SC）的给药被认为是治疗肺动脉高压的一种策略。
本研究报道了含载SC聚（乳酸 - 乙醇酸）纳米颗粒的可吸入微粒的制备。
采用复乳溶剂蒸发法制备SC纳米颗粒。接下来, 在适当的辅料（乳糖、麦芽糖和海藻糖）存在下对游离SC和载SC纳米颗粒进行喷雾干燥。评估所制备粉末的物理化学性质和空气动力学行为。此外，将选定制剂在大鼠肺组织中的药物蓄积情况与口服和静脉给药进行比较。
选定的纳米复合材料和游离SC微粒的粒径和细颗粒分数分别为7和4.5 µm，以及60.2%和68.2%。口服和静脉给药后，分别在4和6小时后肺中检测不到药物，但在载SC纳米颗粒中，即使在吸入1小时后肺中仍可检测到药物。含游离SC的可吸入颗粒起初提供高浓度，吹入后6小时仍可检测到。
体内研究表明，与口服和静脉给药相比，西地那非和西地那非纳米颗粒肺部给药在肺组织中产生更长的半衰期和更高的药物浓度。因此，这些制剂可能比该药物的口服和静脉给药更有效。
