Lipid-microparticles for pulmonary delivery of active pharmaceutical ingredients: Impact of lipid crystallization on spray-drying processability
Spray-drying is an extensively used technology for engineering inhalable particles. Important technical hurdles are however experienced when lipid-based excipients (LBEs) are spray-dried. Stickiness, extensive wall deposition, or simply inability to yield a solid product have been associated to the low melting points of LBEs. In this work, solutions containing polyglycerol esters of behenic acid (PGFA-behenates), or other high melting point LBEs, were spray-dried to produce ibuprofen (IBU)-loaded inhalable lipid-microparticles. Prior to spray-drying, rational boundaries for the outlet temperature of the process were defined using LBE-IBU phase diagrams.
Despite spray-drying the solutions at outlet temperatures below the boundaries, process performance and yield among LBEs were entirely different. Lipid crystallization into polymorphs or multi-phases negatively impacted the yield (10–47%), associated to liquid fractions unable to recrystallize at the surrounding gas temperature in the spray-dryer. The highest yields (76–82%), ascribed to PGFA-behenates, resulted from monophasic crystallization and absence of polymorphism. Lipid-microparticles, composed of a PGFA-behenate, were characterized by a volume mean diameter of 6.586 µm, tap density of 0.389 g/cm3 and corrugated surface. Application as carrier-free dry powder for inhalation resulted in high emitted fraction (90.9%), median mass aerodynamic diameter of 3.568 µm, fine particle fraction of 45.6% and modified release in simulated lung fluid.
Carolina Corzo, Agnes Fuchsbichler, Ioana Savencu, Jesus Afonso Urich, Andreas Zimmer, Dirk Lochmann, Sebastian Reyer, Sharareh Salar-Behzadi,
Lipid-microparticles for pulmonary delivery of active pharmaceutical ingredients: Impact of lipid crystallization on spray-drying processability, International Journal of Pharmaceutics, Volume 610, 2021, 121259, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2021.121259.