Processing-induced-transformations (PITs) during direct compression: impact of compression speeds on phase transition of caffeine

AbstractFor pharmaceutical industry, understanding solid-phase transition of the active pharmaceutical ingredient (API) induced by the manufacturing process is a key issue. Caffeine was chosen as a model API since it exhibits a polymorphic transformation during tableting. This study investigated the impact of the compression speed on the phase transition of anhydrous Form I (CFI) into Form II. Tablets were made from pure CFI and binary mixtures of CFI/microcrystalline cellulose, with an electric press well instrumented at three different compression speeds (50, 500 and 4500 mm min−1). For each velocity of the mobile punch studied, tablets made from three compression pressures (50, 100 and 200 MPa) were analyzed. The determination of the CFI transition degree was performed using a Differential Scanning Calorimetry (DSC). The CFI transition degree was monitored during three months in order to obtain the transformation profile of the API in tablets and in uncompressed powder. The modeling of the profile with...