Mannitol polymorphs as carrier in dpis formulations: isolation characterization and performance

Lactose is still the most commonly used carrier in dry powder inhalers, although some recent studies show that lactose containing DPIs are contraindicated in patients suffering from lactose intolerance. Moreover, lactose is incompatible with drugs that have a primary amine group: this reaction result in the formation of unstable Schiff bases as a consequence of Maillard reaction. For these reasons, a great deal of attention has been posed on mannitol as an alternative carrier for DPIs formulations. Therefore the aim was to produce different polymorphs of mannitol in kinetically stable form and to investigate their solid- state and physico-chemical properties in view of its possible use as a carrier in dry powder inhalers as an alternative to lactose. Once, the kinetically stable form of the mannitol was obtained, the second aim was to investigate the effect of capsule filling parameters on filling process and physico- chemical properties of filling material using in-vitro aerodynamic assessment. Then, the stability and producibility of lysozyme was evaluated in the inhalable formulation containing mannitol were obtained by spray drying technique. The results showed that the lysozyme and new carrier formulation can be obtained by spray drying process and its performance was comparable with mannitol formulation. The PhD project evidenced that it is possible to exploit mannitol a new carrier in formulation for inhalation in which mannitol acts as suitable alternative to lactose for the next generation inhalable products.