Effects of process variables on the powder yield of spray-dried trehalose on a laboratory spray-dryer

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

“…The coefficients of the model equation are negative for gas flow and positive for pump Page 16 of 42 A c c e p t e d M a n u s c r i p t 15 setting and feed concentration, i.e., as gas flow decreases and pump setting and feed concentration increases, particle size increases which is consistent with previous studies 350 (Stähl et al, 2002;Al-Asheh et al, 2003;Maury et al, 2005;Tajber et al, 2009).…”

“…The inlet temperature, as well as the gas flow, had a strong impact on production yields (F-value 74.82, p<0.0001), consistent with results reported by Maury et al (2005) for trehalose spray dried from aqueous solution, where high T inlet resulted in higher T outlet leading to drier and less sticky powders, increasing the 315 production yield. Several interactions among operating variables were detected for trehalose productions yields: two factors, three factors and four factors (involving all main effects); showing how complex the spray drying process is and how one parameter will affect the response from the remaining parameters (Table 3 and Figure 3).…”

“…F-values for these parameters are 229.24 (p<0.0001), 28.87 (p<0.0001) and 4.38 345 (p=0.048), respectively. Maury et al (2005) reported that an increase in pump setting at constant atomizing air flow rate resulted in larger spray droplets, hence larger particles.…”

“…They appear to be effective stabilizers of proteins in the amorphous state (Colaco et al, 1992;Johnson, 1997;Maury et al, 2005). Studies by Lopéz-Diéz et al (2004), Maury et al (2005), Yoshii et al (2008) and Ní Ógáin et al (2011) have established the protective action of trehalose 65 and raffinose on protein integrity, avoiding loss of bioactivity. Crowe (1988, 1989) suggested the water replacement theory to explain the protective action of the sugar compounds, where the formation of H-bonding between the excipient and the biomolecule occurs when water is removed, maintaining the structural integrity of the peptide/protein.…”

“…Maury et al (2005) reported that the most important spray drying parameter to improve trehalose powder yield, for non-porous particles spray dried from aqueous solutions, was the inlet temperature, with the nozzle (a two-fluid nozzle with cap-orifice diameter of 0.7 mm) 110 and aspirator setting have little influence. Ní Ógáin et al (2011) studied the production of trehalose and raffinose nanoporous microparticles (NPMPs) for inhalation, evaluating different ratios of methanol:n-butyl acetate (MeOH:BA) solvent system, and concluded that NPMPs spray dried from 80:20 (v/v) MeOH:BA displayed favourable micromeritic characteristics suggesting potential suitability for pulmonary delivery.…”