(224d) Alcohol Solvates of Sodium Naproxen

Solvents are often used in the production of crystalline pharmaceutical species. During processing, these solvents can become incorporated into the lattice of the crystal in a specific stoichiometric ratio to form solvates or hydrates (also known as pseudopolymorphs). The properties of pseudopolymorphs differ from those of the unsolvated species, which should not be surprising because their compositions are different. Solvate formation has become increasingly important for several technical and industrial reasons, such as purification, preparation of a specific polymorph with high chemical and physical purity, or particle size control due to the fact that desolvation of stoichiometric solvates often leads to products with a small and homogenous particle size distribution. With the increasing number of solvate discoveries, their importance in terms of intellectual property is also increasing.

Sodium naproxen is a non-steroidal, anti-inflammatory drug that has been shown to exhibit five pseudopolymorphic forms (anhydrous, monohydrated, dihydrated, tetrahydrated, and a methanol solvate). The purpose of the present study is to examine organic alcohol solvates of sodium naproxen. Using batch cooling crystallization to an equilibrium temperature of 10°C, alcohol solvates of ethanol, 1-propanol, 2-propanol, 1-butanol, and isobutanol were discovered. The present study relates the formation of sodium naproxen solvates to the the size and branching of the solvent molecule. Thermal gravimetric analysis and differential scanning calorimetry were especially important tools in exploring properties of the solvates. The habits of solvate crystals varied considerably with solvating species and these were examined and compared to previously known pseudopolymorphs of sodium naproxen.