Safinamide mesylate (SAFIM) is a drug used in its anhydrous form as an add-on treatment for Parkinson′s disease. This work demonstrates the feasibility of a spherical agglomeration process on a molecule exhibiting an agglomeration′s unfavorable crystalline landscape, due to the high stability of SAFIM hydrate. After a comprehensive characterization of the crystalline landscape of SAFIM, conditions to obtain anhydrous SAFIM during the agglomeration process are presented. Temperature, stirring rate, the concentration of the slurry, and the amount of bridging liquid were studied to obtain spherical agglomerates with desirable micromeritic properties.

The dehydration of prednisolone sesquihydrate is studied and characterized by different physico-chemical analysis methods. The meticulous study of this dehydration led to the highlighting of a new solid form (form 3), metastable, never identified before. In a second step, the rehydration of anhydrous forms 1 and 2 of prednisolone is studied, in particular by Dynamic Vapor Sorption. It is then demonstrated that neither of the two forms is sensitive to humidity. By means of solid-gas equilibria, the sesquihydrate can only be obtainable from the isomorphic anhydrous form. Finally, a classification of the sesquihydrate is made, taking into account, in particular, the activation energy determined during dehydration.

Since more and more pharmaceutical substances are developed as amorphous forms, it is nowadays of major relevance to get insights into the nucleation and growth mechanisms from supercooled melts (SCM). A step-by-step approach of recrystallization from a SCM is presented here, designed to elucidate the impact of various experimental parameters. Using the bronchodilator agent Diprophylline (DPL) as a model compound, it is shown that optimal conditions for informative observations of the crystallization behaviour from supercooled racemic DPL require to place samples between two cover slides with a maximum sample thickness of 20µm, and to monitor recrystallization during an annealing step of 30min at 70°C, i.e. about 33°C above the temperature of glass transition. In these optimized conditions, it could be established that DPL crystallization proceeds in two steps: spontaneous nucleation and growth of large and well-faceted particles of a new crystal form (primary crystals: PC) and subsequent crystallization of a previously known form (RII) that develops from specific surfaces of PC. The formation of PC particles therefore constitutes the key-step of the crystallization events and is shown to be favoured by at least 2.33wt% of the major chemical impurity, Theophylline.