Polymorphic Transformations and in Vitro Bioequivalence Assessment of Saxagliptin Hydrochloride Solid Forms

Abstract

Saxagliptin hydrochloride, a dipeptidyl peptidase-4 (DPP-4) inhibitor widely used in the treatment of type 2 diabetes mellitus, can exist in multiple polymorphic forms that may significantly influence its physicochemical and biopharmaceutical properties. Polymorphism plays an important role in determining drug solubility, dissolution rate, stability, and ultimately its bioavailability. Therefore, understanding the polymorphic behavior of saxagliptin hydrochloride is essential to ensure consistent drug performance and therapeutic effectiveness. The present study investigates the polymorphic transformations of saxagliptin hydrochloride and evaluates their impact on in vitro bioequivalence. Different solid forms of saxagliptin hydrochloride were prepared and subjected to polymorphic transformation studies under controlled environmental and processing conditions. The obtained polymorphs were characterized using analytical techniques including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These characterization methods were employed to identify variations in crystalline structure, thermal properties, and molecular interactions among the different solid forms. Furthermore, in vitro dissolution studies were conducted under simulated gastrointestinal conditions to evaluate the pharmaceutical performance of each polymorphic form. Dissolution profiles were analyzed and compared using model-independent approaches to determine similarity and assess their bioequivalence potential. The results indicate that variations in crystal structure can influence the dissolution behavior of saxagliptin hydrochloride, which may subsequently affect its absorption characteristics. Overall, the findings emphasize the significance of polymorphic control during pharmaceutical development and manufacturing processes. A detailed understanding of polymorphic transformations assists in selecting the most stable and pharmaceutically suitable solid form, ensuring consistent dissolution performance and reliable therapeutic outcomes. In addition, in vitro bioequivalence studies provide an effective approach for evaluating the impact of polymorphism on drug formulation and quality control.