On the compaction behaviour of different physical forms of a new API

FRX112 is a new drug under development, which is affected by poor compaction properties. Aim of this work was to seek different physical forms (in terms of crystal habit, particle size, polymorphism and pseudopolymorphism) with improved tableting features.FRX112 starting material (anhydrate, A) was suspended in water (3 hours, room temperature); the resulting solid phase (H) was treated at 100°C for 15 min and form A* was obtained. All solid phases were characterized for their physical properties (PXRD, DSC, TGA, KF titration, SEM, particle size distribution and compaction behaviour). Compaction studies were performed on powder samples (250mg) manually loaded into the die of a rotary instrumented tableting machine equipped with round (11mm diameter) flat punches. The punches setup was progressively varied so that the minimal distance between upper and lower punches ranged from 1.95 to 2.55mm. Compaction forces at the upper punch (Fs) and crushing force (Fc) of the compacts were recorded.Suspension of A (needle-shaped crystals, Dvs=11.76&[mu]m) in water produced a new, stable hemihydrate phase, H (needle-shaped crystals, Dvs=6.84&[mu]m). On heating under controlled conditions, H dehydrates to anhydrous phase (A*), showing (i) the same crystal structure of A, (ii) particle size (Dvs= 6.76&[mu]m) similar to that of H and (iii) the same crystals morphology of A and H. With tableting machine setup and sample mass being equal, similar Fs values were recorded irrespective of the physical form; the hardness (Fc) of the resulting compacts followed the order A*>A~H. The overall behaviour suggests superior ability of the anhydrate in establishing effective cohesion between particles. Difference in Fc of A and A* compacts can be obviously ascribed to the different particle size.A hemihydrate and an anhydrous form of FRX112 are described and compared in terms of compaction behaviour. The anhydrous form is recommended for tableting purposes.