Celecoxib sodium salt: engineering crystal forms for performance

作者：Remenar Julius F^*; Tawa Mark D; Peterson Matthew L; Almarsson Oern; Hickey Magali B; Foxman Bruce M

来源：CrystEngComm, 2011, 13(4): 1081-1089.

DOI：10.1039/c0ce00475h

Crystalline hydrates and propylene glycol solvates of celecoxib sodium salt (Cel-Na) were prepared and characterized with the aim of improving oral drug absorption by breaking up the H-bonding interactions present in crystals of the poorly soluble marketed form of the drug (Cel-III). The hydrate grows rapidly from aqueous alkaline solution, forming a thick slurry of thin plates. Thicker plates for structure determination were successfully grown by adding up to 1% benzyl alcohol to the solution. The structure of the pentahydrate of the sodium salt is comprised of a bilayer motif where three waters are coordinated to sodium ions in a discrete layer, while the other two waters reside in a one-dimensional channel. At a given temperature, the hydration state changes rapidly and reversibly as a function of relative humidity (RH). The hydrated salt is physically stable in a sealed vial, but reverts rapidly to the crystalline free base if exposed to ambient CO2 in air at 40% RH or higher. The propylene glycol (PG) solvate of Cel-Na exists in an anhydrous and trihydrate form. The trihydrated PG solvate of Cel-Na is physically stable above similar to 15% RH and does not react measurably with CO2 at 66% RH over 4 days, making it the most suitable form for use in solid pharmaceutical formulations.

• 出版日期2011