Optimisation of spray drying process conditions for sugar nanoporous microparticles (NPMPs) intended for inhalation

Abstract

The present study investigated the effect of operating parameters of a laboratory spray dryer on powder characteristics, in order to optimise the production of trehalose and raffinose powders, intended to be used as carriers of biomolecules for inhalation.The sugars were spray dried from 80:20 methanol:n-butyl acetate (v/v) solutions using a 30Büchi Mini Spray dryer B-290. A 2 4 factorial design of experiment (DOE) was undertaken. Process parameters studied were inlet temperature, gas flow rate, feed solution flow rate (pump setting) and feed concentration. Resulting powders where characterised in terms of yield, particle size (PS), residual solvent content (RSC) and outlet temperature. An additional outcome evaluated was the specific surface area 35 (SSA) (by BET gas adsorption), and a relation between SSA and the in vitro deposition of the sugar NPMPs powders was also investigated.The DOE resulted in well fitted models. The most significant factors affecting the characteristics of the NPMPs prepared, at a 95% confidence interval, were gas flow:yield, PS and SSA; pump setting: yield; inlet temperature: RSC. 40Raffinose NPMPs presented better characteristics than trehalose NPMPs in terms of their use for inhalation, since particles with larger surface area resulting in higher fine particle fraction can be produced. 45

Formulation, stability and pharmacokinetics of sugar-based salmon calcitonin-loaded nanoporous/nanoparticulate microparticles (NPMPs) for inhalation

“…Table 1 describes in detail the composition of the spray dried solutions. Nitrogen (at 6 bar) was used as the drying gas in a co-current mode. Spray drying parameters were set as for optimised raffinose and trehalose NPMP production, as previously described (Amaro et al, 2011). Spray dried particles were separated from the drying gas using a high-performance cyclone (Büchi, Switzerland).…”

“…The samples were fixed on aluminum stubs using double-sided adhesive tape and sputtercoated with gold. Visualisation was performed at 5 kV and photo micrographs were taken at different magnifications in more than one region of the sample, as reported by Amaro et al (2011Amaro et al ( , 2014.…”

“…The particle size (PS) distributions of the spray-dried powders were determined using a Mastersizer 2000 laser diffraction instrument (Malvern Instruments, UK) with a dry powder sample dispersion accessory (Scirocco 2000) as previously reported by Ní Ógáin et al (2011) and Amaro et al (2011Amaro et al ( , 2014. Samples were run in triplicate.…”

“…We have previously reported on the optimisation of a spray drying method to produce raffinose and trehalose nanoporous/ nanoparticulate microparticles and the formulation enhancement of these powders by inclusion of hydroxypropyl-b-cyclodextrin (Amaro et al, 2011(Amaro et al, , 2014.…”

“…The NPMP technology has been well characterised by Healy et al (2008); Nolan et al (2011);Ní Ógáin et al (2011);Amaro et al (2011Amaro et al ( , 2014, with spray dried powders displaying favourable micromeritic characteristics, suggesting potential suitability for pulmonary delivery. More recently a novel morphology classification system for porous microparticles was introduced by Paluch et al (2012) and is applied in the present study.…”