SPHERICAL CRYSTALLIZATION OF SITAGLIPTIN PHOSPHATE MONOHYDRATE FOR FORMULATION OF DIRECTLY COMPRESSIBLE TABLETS

Sitagliptin was invented in 2006 as a DPP-4 inhibitor. It is soluble in water to the extent of 0.03 mg/mL as thus suffers bioavailability problems. It was converted into phosphate monohydrate salt with solubility 50 mg/mL, which solved bioavailability problems. In this research, an attempt is made to convert it from its crystalline form into spherical crystals. Spherical crystals have better bulk properties and can adapt to direct compression tableting. This kind of innovation saves the time needed for granulation and can be compressed directly just by adding lubricant and disintegrant. In this research sitagliptin, phosphate monohydrate was made as spherical crystals using water as a solvent, ethanol as anti-solvent, and chloroform as bridging liquid. 3² factorial designs for optimization was applied to get an optimized batch with a concentration of bridging liquid and anti-solvent as independent and Carr’s index and yield as dependent variables. Batch F7 was considered optimized with a yield of 97.5%. Spherical crystals thus obtained were characterized using X-Ray diffraction, SEM, % compressibility, and flowability. The spherical crystals were directly compressible after adding 8% SSG and 2% magnesium stearate. The resultant tablets were film-coated using HPMC 2910. It was compared with a marketed film-coated tablet, both having a 50 mg dose of sitagliptin phosphate monohydrate, with encouraging results. Thus it can be concluded that the aim of the research: spherical crystallization of sitagliptin phosphate monohydrate for the formulation of directly compressible tablets is fulfilled.