Solid-State Characterization of Different Crystalline Forms of Sitagliptin

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Active pharmaceutical ingredient (API) solid-state properties, including polymorphism, solvates, and hydrates, critically influence drug product performance.
• Physicochemical characterization of APIs is essential for developing safe and effective pharmaceutical dosage forms.
• Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is widely used for type 2 diabetes mellitus treatment.

Purpose of the Study:

• To conduct a comprehensive solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous, and sitagliptin base form.
• To evaluate the impact of crystalline form on the physicochemical properties and thermal behavior of sitagliptin.
• To identify the most suitable crystalline form for pharmaceutical formulation development.

Main Methods:

• Differential scanning calorimetry (DSC) and thermogravimetry (TG)/derivative thermogravimetry (DTG) for thermal analysis.
• Spectroscopic techniques and X-ray powder diffraction (XRPD) for structural and crystalline phase identification.
• Scanning electron microscopy (SEM) for morphological analysis.

Main Results:

• Sitagliptin phosphate monohydrate undergoes a crystalline transition during dehydration, affecting its melting point and solubility.
• Sitagliptin base form exhibits a lower melting point (120.29 °C) compared to its phosphate counterparts.
• Sitagliptin phosphate anhydrous (214.92 °C) and monohydrate (206.37 °C) demonstrate superior thermal stability over the base form, with slight differences between the two phosphate forms.

Conclusions:

• The crystalline form significantly impacts sitagliptin's physicochemical properties, including thermal stability and melting behavior.
• Sitagliptin phosphate anhydrous and monohydrate exhibit enhanced thermal stability, making them preferable for pharmaceutical development.
• This study provides crucial data for selecting the optimal crystalline form of sitagliptin to ensure a safe, effective, and stable pharmaceutical dosage form.