Sildenafil citrate monohydrate–cyclodextrin nanosuspension complexes for use in metered-dose inhalers

摘要: Sildenafil is a selective phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. citrate monohydrate was complexed with α-, hydroxypropyl-β- γ-cyclodextrin (α-CD, HP-β-CD γ-CD, respectively) to enhance its water solubility. The complexes sildenafil all types CDs were characterized by phase solubility diagrams, (1)H (13)C NMR, dielectric constants. developed as nanosuspensions use in pressurized metered-dose inhaler (pMDI). pMDI formulations prepared bottom-up process using dried ethanol solvent HFA-134a an antisolvent propellant order form nanosuspensions. A 3×3 factorial design applied contents propellant. profiles cyclodextrins described AL type mole ratio 1:1. piperazine moiety formed inclusion cavity CDs. particle diameters suspensions pMDIs within nanosuspension size range. An assay content showed that formation close 100%. In case CDs, emitted doses varied 97.4±10.8%, fine fractions (FPFs) range 45-81%, dose (FPD) 12.6±2.0 μg mass median aerodynamic (MMADs) 1.86±0.41 μm. contrast, without produced low (<60%). Therefore, only containing suitable aerosols.