Lipid-microparticles for pulmonary delivery of active pharmaceutical ingredients: Impact of lipid crystallization on spray-drying processability.

Autor: Corzo C; Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Graz, Austria., Fuchsbichler A; Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Graz, Austria., Savencu I; Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Afonso Urich J; Research Center Pharmaceutical Engineering GmbH, Graz, Austria., Zimmer A; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Graz, Austria., Lochmann D; IOI OLEO GmbH, Witten, Germany., Reyer S; IOI OLEO GmbH, Witten, Germany., Salar-Behzadi S; Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Graz, Austria. Electronic address: sharareh.salar@rcpe.at.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2021 Dec 15; Vol. 610, pp. 121259. Date of Electronic Publication: 2021 Nov 02.
DOI: 10.1016/j.ijpharm.2021.121259
Abstrakt: 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/cm 3 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.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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