Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy

Abstract

Abstract. Moisture content and aerodynamic particle size are critical quality attributes for spray-dried protein formulations. In this study, spray-dried insulin powders intended for pulmonary delivery were produced applying design of experiments methodology. Near infrared spectroscopy (NIR) in combination with preprocessing and multivariate analysis in the form of partial least squares projections to latent structures (PLS) were used to correlate the spectral data with moisture content and aerodynamic particle size measured by a time of flight principle. PLS models predicting the moisture content were based on the chemical information of the water molecules in the NIR spectrum. Models yielded prediction errors (RMSEP) between 0.39% and 0.48% with thermal gravimetric analysis used as reference method. The PLS models predicting the aerodynamic particle size were based on baseline offset in the NIR spectra and yielded prediction errors between 0.27 and 0.48 μm. The morphology of the spray-dried particles had a significant impact on the predictive ability of the models. Good predictive models could be obtained for spherical particles with a calibration error (RMSECV) of 0.22 μm, whereas wrinkled particles resulted in much less robust models with a Q 2 of 0.69. Based on the results in this study, NIR is a suitable tool for process analysis of the spray-drying process and for control of moisture content and particle size, in particular for smooth and spherical particles.

Human αB-crystallin as fusion protein and molecular chaperone increases the expression and folding efficiency of recombinant insulin

“…For each dried sample, the NIR spectra were recorded through the bottom of the glass plate. To decrease the possible effect of uneven distribution of dried insulin, the protein samples were rotated and measured again [ 36 ]. Each spectrum consisted of the average of 3 replicates.…”

Solvent-Free Melting Techniques for the Preparation of Lipid-Based Solid Oral Formulations

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1H NMR quantification of spray dried and spray freeze-dried saccharide carriers in dry powder inhaler formulations

“…Particles collected from the low impactor stages (e.g., between 3 and 5) with less than or equal to 5.0 µm aerodynamic diameter generally represent the respirable-sized drug dose, whereas particles deposited in the higher impactor stages (e.g., throat and stage 1) represent the oropharyngeal deposition in the oropharynx region (Niwa, Mizutani and Danjo, 2012;Ali and Gary, 2015). In order to achieve therapeutic efficacy, the size of drug particles should be respirable (MMAD ≤5.0 µm) with low GSD indicating monodisperse particle size distribution to reach the desired deep lung regions for systemic pulmonary delivery and FPF should be high for drug aerosolisation efficiency (Kramek-Romanowska et al, 2011;Maltesen, Weert and Grohganz, 2012;Walters et al, 2014;Yang, Chan and Chan, 2014;Rahimpour, Kouhsoltani and Hamishehkar, 2014;Ali and Gary, 2015;Banga, 2015;Peng et al, 2016).…”