Nitrofurantoin-p-aminobenzoic acid cocrystal: Hydration stability and dissolution rate studies

Abstract

Nitrofurantoin (NF) drug is known to transform to a hydrate form in aqueous medium. The hydration stability and dissolution rate of a few cocrystals of NF were compared with that of its stable β polymorph and hydrate form II. Hydrogen bonding and molecular packing in the novel cocrystal structures were analyzed. Pharmaceutical cocrystals of NF with p-aminobenzoic acid (PABA) and urea showed superior physicochemical properties compared with the known l-arginine salt hydrate. All the solid-state adducts were characterized by single-crystal X-ray diffraction, X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis. NF-PABA cocrystal was found to be superior among the compounds studied in terms of minimal transformation to NF hydrate and comparable dissolution rate to the reference drug. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association.