Ahmadreza Barazesh1, Kambiz Gilani2,3, Mohammadreza Rouini4, Mohammad Ali Barghi5. 1. Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2. Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. gilani@tums.ac.ir. 3. Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran. gilani@tums.ac.ir. 4. Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 5. XRD Research Laboratory, School of Science, University of Tehran, Tehran, Iran.
Abstract
PURPOSE: Metal salts are used in formulation of dry powder inhalers (DPIs) for different purposes. Recently the role of these salts in production of small, dense but highly dispersible particles has emerged. In this study the effect of some such salts on dispersibility and respirability of spray dried levofloxacin formulations was evaluated in normal and reduced inhalation air flow or by increasing powder filling in capsules. METHODS: levofloxacin was co-spray dried with different concentrations of common metal chlorides (NaCl, KCl, CaCl2 and MgCl2) either with or without leucine as dispersibility enhancer. Particle size, moisture, morphology, triboelectrification tendency and fine particle fraction (FPF) of resulting powders were evaluated. In addition, the effect of these salts and leucine on dispersibility of resulting powders in reduced air flow rate and increased capsule filling mass were evaluated. RESULTS: Presence of higher tested concentrations of divalent cations increased water content, and reduced FPF significantly. Addition of leucine reduced water content and electrostatic charge, increased particle size and FPF and improved spray drying yield significantly. Lower concentrations of salts did not affect FPF of leucine containing powders significantly, but presence of 2.5% NaCl or MgCl2 preserved the dispersibility in higher capsule fillings. A 2.5% concentration of NaCl in such formulations preserved dispersibility in lower air flows. CONCLUSION: Higher amounts of divalent salts increases triboelectrification and moisture absorption, and reduces FPF. Lower concentrations of NaCl could not improve FPF of leucine containing formulations significantly, but preserves dispersibility in low air flows and high capsule fillings. Graphical abstract.
PURPOSE: Metal salts are used in formulation of dry powder inhalers (DPIs) for different purposes. Recently the role of these salts in production of small, dense but highly dispersible particles has emerged. In this study the effect of some such salts on dispersibility and respirability of spray dried levofloxacin formulations was evaluated in normal and reduced inhalation air flow or by increasing powder filling in capsules. METHODS:levofloxacin was co-spray dried with different concentrations of common metal chlorides (NaCl, KCl, CaCl2 and MgCl2) either with or without leucine as dispersibility enhancer. Particle size, moisture, morphology, triboelectrification tendency and fine particle fraction (FPF) of resulting powders were evaluated. In addition, the effect of these salts and leucine on dispersibility of resulting powders in reduced air flow rate and increased capsule filling mass were evaluated. RESULTS: Presence of higher tested concentrations of divalent cations increased water content, and reduced FPF significantly. Addition of leucine reduced water content and electrostatic charge, increased particle size and FPF and improved spray drying yield significantly. Lower concentrations of salts did not affect FPF of leucine containing powders significantly, but presence of 2.5% NaCl or MgCl2 preserved the dispersibility in higher capsule fillings. A 2.5% concentration of NaCl in such formulations preserved dispersibility in lower air flows. CONCLUSION: Higher amounts of divalent salts increases triboelectrification and moisture absorption, and reduces FPF. Lower concentrations of NaCl could not improve FPF of leucine containing formulations significantly, but preserves dispersibility in low air flows and high capsule fillings. Graphical abstract.