Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles
Samaneh Alaei, Elham Ghasemian, Alireza Vatanara
Abstract
Size reduction to a nanoscale is a relatively new approach to overcome solubility and bioavailability issues of many drugs such as cefixime (CFX). However, nanoparticles and specifically nanosuspensions are prone to many instabilities like aggregation and sedimentation. One of the main solutions is transforming liquid nanosuspension into dry powder. In this study, cefixime (CFX) nanosuspension was co-spray dried in the presence of different carriers (lactose, mannitol and sorbitol) in 3 ratios of nanoparticles (NPs)/carriers (1, 1.5 and 4 (w/w)). Physicochemical properties of the obtained powders were assessed in terms of particle size, morphology, thermal behavior, flowability, dissolution profile and aggregation over 6 months. Co-processing of NPs resulted in the formation of partially spherical particles with deeply wrinkled surfaces in the sizes ranging from 3.61 to 12.18 μm. Flowability showed improvement of all microparticles and thermal analysis demonstrated an amorphous state. Results suggest that among carriers, sorbitol based microparticles had the same dissolution profile as the initial NPs (29-fold increase in maximum solubility compared to unprocessed CFX) and could preserve reconstituted NPs’ size efficiently after storage. This shows the feasibility of using sorbitol as a promising carrier for spray drying of nanosuspensions which was mostly used for co-processing of solid lipid nanoparticles, proteins and peptides before.