Dry Powder Formulation of Simvastatin Nanoparticles for Potential Application in Pulmonary Arterial Hypertension
It has been hypothesized that simvastatin could be used to treat pulmonary arterial hypertension (PAH). This study is intended to formulate a simvastatin nanoparticle dry powder inhalation (DPI) formulation. Simvastatin nanoparticles were prepared via an emulsification and homogenization-extrusion method, followed by spray drying of the colloidal suspension of simvastatin nanoparticles containing mannitol to get it into a respirable size. Particle size distribution, morphology, and crystallinity of the fabricated nanoparticles of the obtained microparticles for DPI formulation were assessed by dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray diffraction pattern (XRPD), respectively. Aerosolization performance of the DPI formulation was assessed by the Next Generation Impactor (NGI) equipped with an Aerolizer®.
Simvastatin nanoparticles were around 100 nm with a very narrow size distribution (PDI = 0.105). The X-ray diffraction pattern revealed that the crystallinity of simvastatin was decreased by the spray drying procedure. Microscopic images displayed that gathered nanoparticles were in the suitable inhalable range and had the appropriate shape and surface properties for pulmonary delivery. Aerosolization assessment by the NGI indicated a suitable inhalation performance (fine particle fraction of 20%). In conclusion, the results confirmed that the spray drying technique for simvastatin can be optimized to obtain simvastatin aggregated nanoparticles without any coarse carrier to be used in DPI formulation for better deposition of the drug in the lungs for local treatment of PAH.
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Simvastatin was supplied from Aria Ltd. (Tehran, Iran). Chloroform, acetonitrile, and methanol were purchased from Duksan Pure Chemicals (Ansan, Korea). Soybean phosphatidylcholine (SPC, purity >99%) was acquired from Lipoid GmbH (Ludwigshafen, Germany). D-Mannitol and ethanol were obtained from Fluka (Steinheim, Germany) and JATA (Iran) companies respectively. Tween® 80, span® 80, polyvinyl alcohol (PVA), and polyethylene glycol (PEG) 400 were acquired from Sigma-Aldrich (St Louis, MO, USA).
Zendehdel Baher, S.; Yaqoubi, S.; Asare-Addo, K.; Hamishehkar, H.; Nokhodchi, A. Dry Powder Formulation of Simvastatin Nanoparticles for Potential Application in Pulmonary Arterial Hypertension. Pharmaceutics 2022, 14, 895. https://doi.org/10.3390/pharmaceutics14050895