Formulation and evaluation of inhalable microparticles of Rizatriptan Benzoate processed by spray freeze-drying

Abstract

The aim of the current study was to prepare and evaluate inhalable microparticles of Rizatriptan benzoate in order to further benefit from its pulmonary delivery, the expected enhanced bioavailability and accelerated onset of action. The spray freeze drying (SFD) technique was used to produce microparticles consisting of a fixed amount of a sugar which was either mannitol or trehalose and an amino acid component including leucine, phenylalanine or serine. The powders were then characterized for particle size distribution, morphology, thermal properties and in vitro aerosolization performance. It was demonstrated that various formulations of inhalable Rizatriptan could be efficiently aerosolized and offered acceptable fine particle fraction (FPF) ranging up to 61.1. In particular, a spray-freeze-dried powder composed of trehalose and phenylalanine showed the most superior inhalation performance (FPF = 61.1), indicating better dispersion properties of those spherical porous microparticles with less adhesion and agglomeration. These results successfully demonstrated that Rizatriptan could be engineered into respirable microparticles to be proposed as a promising delivery system for fast and effective control of migraine attacks. © 2021 Elsevier B.V