Development of dry powder inhaler containing tadalafil-loaded PLGA nanoparticles

Abstract

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 in vitro 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.

Experimental evaluation of furosemide and/or tadalafil in conventional and nanoparticle forms in prevention of chronic renal failure induced in rats.

“…2.4 Preparation of poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with tadala l Tadala l loading NPs were kindly provided by the National Research Center (NRC), Cairo, Egypt. Tadala lloaded NPs were prepared according to the solid-in-oil-in-water (s/o/w) emulsion technique [12]. PLGA (35 mg) was dissolved in dichloro-methane for 6 h to obtain a uniform PLGA solution.…”

Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension

“…Prostacyclin (PGI 2 ) analogue [27,28,29,30], PDE5 inhibitors [31,32], ERA [33], oligonucleotides [34,35], pitavastatin [36,37], imatinib [38], rapamycin [39], and fasudil [40]-loaded NPs have been reported to be effective in animal PAH models and in vitro studies (Table 1). All of the data in the studies were obtained in animal models of PAH or in vitro studies and have not yet been translated to human trials.…”

Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization

“…On this basis, the current work endeavors for the first time-to the best of our knowledge-to develop TD-NEs that can resist aqueous dilution to be used for the treatment of pediatric PAH via nebulization using a jet nebulizer. Nanoparticles, microspheres, and nanocomposites of TD have been previously developed as inhalable dry powders for treating PAH [26][27][28]. However, it has been reported that dry powder formulations encounter problems during powder processing and re-dispersion (adhesion and strong agglomeration), which makes them unsuitable for efficient inhalation [10].…”