Title : Analytical strategies for solid-state forms in drug development
Abstract:
The solid-state characterization of pharmaceutical compounds plays a pivotal role in understanding and controlling the physical and chemical properties of active pharmaceutical ingredients (APIs) and excipients. This work presents an integrated overview of analytical techniques applied to solid-state forms, including polymorphs, hydrates, solvates, and amorphous systems. Key methods such as powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and vibrational spectroscopy (FT-IR, Raman, and hot-stage Raman) are discussed for their diagnostic value in identifying crystal structures, phase transitions, and dehydration/solvation processes. Surface-enhanced Raman spectroscopy [SERS]) are explored for their potential in elucidating molecular packing, surface morphology, and solid-solid transitions. The combination of these tools provides a robust analytical platform for form selection and stability assessment. Selected case studies—such as the polymorphic forms of chloramphenicol palmitate, hydration states of ampicillin, and thermal behavior of tamoxifen citrate—demonstrate the practical application of multitechnique approaches. Emphasis is placed on the importance of coupling conventional characterization with chemometric and predictive modeling strategies to meet regulatory requirements and enhance the reliability of solid-state analysis in drug development.
