Solid-State Dehydration Mechanism of Diclofenac Sodium Salt Hydrates

Salt formation is a useful technique for improving the solubility of active pharmaceutical ingredients (APIs). For instance, nonsteroidal anti-inflammatory drug, diclofenac (DIC), used in sodium salt form, and it has been reported to form several hydrate forms. However, crystal structure anhydrous (DIC-Na) structural relationship among anhydrate hydrated forms have not yet revealed. In this study, DIC-Na was analyzed using single-crystal X-ray diffraction (XRD). To determine solid-state dehydration/hydration mechanism hydrates based on both present previously structures (4.75-hydrate 3.5-hydrate), additional experiments including simultaneous powder XRD differential scanning calorimetry, thermogravimetry, dynamic vapor sorption measurements, comparison were performed. The dehydration 4.75-hydrate found occur two steps. During first step, only water molecules that coordinated Na+ ions lost, which led 3.5-hydrate while retaining alternating layered structures. subsequent step into phase accompanied substantial reconstruction. This study elucidated complete landscape transformation time through investigation. These findings contribute understanding underlying these phenomena physicochemical properties crystals.