Advanced Design and Development of Novel Microparticulate/Nanoparticulate Dry Powder Inhalers for Targeted Treatment of Pulmonary Hypertension
AuthorAcosta, Maria Fernanda
KeywordsPharmaceutics and Pharmacokinetics
AdvisorMansour, Heidi M.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
EmbargoRelease after 05/02/2020
AbstractPulmonary drug delivery is rapidly becoming one of the most important routes for targeting drugs to treat respiratory diseases. Pulmonary hypertension (PH) is a life-threatening disease characterized by an increase in pulmonary artery pressure. PH is complex and multifactorial making a challenge to researchers for the understanding of molecular mechanisms that are involved in the pathogenesis and the developing of novel pharmacological strategies to treat this disease. The objective of this study was to design targeted dry powder inhalers (DPIs) for the treatment of this fatal disease using new active pharmaceutical ingredients (APIs) which trigger novel molecular and cellular mechanisms of the disease. Dry powder inhalable microparticles/nanoparticles of Simvastatin (Sim), L-Carnitine (L-Car), L-Carnitine (HCl), Metformin (Met) and a combination of Sim and L-Car HCl were developed using the advanced spray drying (SD) technique in closed mode. This particle engineering technique offers many advantages such as the ability to tailor particle properties and characteristics for the appropriate deposition of the DPIs into the lungs. Many analytical techniques were utilized in this dissertation to perform the physicochemical characterization of the achieved powders. The Next Generation Impactor (NGI™) and different human FDA approved DPI devices were employed to evaluate the in vitro aerosol dispersion performance of the DPIs. The results were statistically analyzed and correlated with the microscopic and macroscopic properties of the powders. Different in vitro cell models such as 2-D vs. 3-D in liquid covered conditions vs. air-liquid interface conditions were employed to test the drug-response and safety of the powder formulations. Different in vivo models in healthy and diseased animals were used to test our DPIs. After this extensive study, it was concluded that the formulated DPIs showed promising results to treat PH.
Degree ProgramGraduate College