Propagation of Solid-State Transformations by Dehydration and Stabilization of Pseudopolymorphic Crystals of Sodium Naproxen

Abstract

The presence of water molecules in the crystal structure of a pharmaceutical compound greatly affects its properties. Therefore, hydration and dehydration are among the most important reactions in the pharmaceutical industries. Sodium naproxen is an antiinflammatory nonsteroidal drug used to treat moderate pain, osteoarthritis, rheumatoid arthritis, and other conditions. Dehydration of powderlike dihydrated sodium naproxen was examined to determine the course of dehydration of the dihydrated species and the relative stability of three pseudopolymorphs: dihydrated, monohydrated, and anhydrous sodium naproxen. During the dehydration, no intermediate crystal structure was detected by powder X-ray diffraction (PXRD), and no polymorph or pseudopolymorph other than the three mentioned was observed. Furthermore, scanning electron microscopy (SEM) revealed enormous cracks that were aligned along the c-axis of the monohydrate on the surface of the dehydrated species obtained from dehydration of monohydrated single crystals. Comparison of unit cells of the monohydrated and the anhydrous sodium naproxen showed structural similarity. Hydrogen bonds are very important in stabilizing the packing of the monohydrate, while Na−O type interactions stabilize the packing of the anhydrous species.