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Investigations on Polymorphism of Mannitol/ Sorbitol Mixtures after Spray-drying using Differential Scanning Calorimetry, X-ray Diffraction and Near-Infrared Spectroscopy

Heike Bauer a , Thorsten Herkert b , Matthias Bartels c , Karl-Artur Kovar b , Eugen Schwarz c , and Peter Christian Schmidt

a Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences a , Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences b , Eberhard-Karl University, Tübingen (Germany), and Merck KGaA c , Darmstadt (Germany)

The purpose of this study was to determine the crystallisation behaviour of the two sugar alcohols mannitol and sorbitol and stability thereof after spray-drying aqueous solutions of mannitol/sorbitol-mixtures (ranging from 10 to 40 % of sorbitol in the formulations). By means of Differential scanning calorimetry and X-ray powder diffraction the effects observed in melting behaviour and crystal structures as consequences of spray-drying and storage conditions were investigated. Using Near-Infrared spectroscopy it was possible to take a closer look at the polymorphism of each compound. Neither cocrystals nor eutectic mixtures were obtained. The components crystallise separately. Concerning sorbitol mainly a solidified melt is harvested, besides some amorphous material, which transforms into the ß- and a-modification during storage. Mannitol was determined to crystallise as ß-mannitol accompanied by little amounts of the a-polymorph. This constellation turned out to be stable. The co-spray-dried formulation was extremely sensitive to increased humidity.

Key words Analytics · Mannitol · Polymorphism · Sorbitol · Spray-drying · Stability