A multivariate approach applied to quality on particle engineering of spray-dried mannitol

• First study using response surface methodology to spray drying of mannitol.
• Outlet temperature affected particle shape.
• Mannitol solubility in solvent governed mean particle size.
• Mannitol concentration affected particle size distribution.
• Optimized spray dried mannitol properties were obtained by desirability functions.

Box-Benhken design was applied to engineer spray dried mannitol particles. Particles were characterized by optical microscopy to determine size, size distribution, shape and morphology comparing to a reference material commercially available. Two shape factors calculated with the results of image analysis, circularity and projected area equivalent diameter (Heywood diameter), as well as span value for size distribution, were chosen as responses for analyses of variance. Outlet temperature was shown to be the most important factor to control during the process in order to produce particles with high value of circularity. Particle size represented as Heywood diameter was affected by ethanol while particle size distribution was affected by concentration of mannitol solution. Desirability function was applied to determine the best process parameters and to predict the responses, which were confirmed experimentally. Morphology was evaluated with scanning electron microscopy and confirmed results of ANOVA for circularity, showing that regulars and spherical particles were produced at low temperature. FTIR and DRX were used to demonstrate that particles did not modify polymorph after the spray drying keeping the same β-form of the raw mannitol.

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