Synthesis, Structural, and Physicochemical Insights of Novel Cocrystals of Zaleplon

Abstract

Zaleplon (ZLP, BCS class II) is a hypnotic drug used to treat insomnia having a low intrinsic dissolution rate (IDR) and poor bioavailability due to its low water solubility. The cocrystallization technique is adopted to produce novel solid forms (salts/cocrystals) of drugs to improve their physicochemical properties such as solubility, stability, IDR, and bioavailability. Herein, we used organic acids to synthesize novel cocrystals of ZLP with increased water solubility and IDR. Single-crystal and powder X-ray diffraction and differential scanning calorimetry (DSC) were used to characterize the cocrystals. The solubility, IDR, and partition coefficient (between water and n-octanol) of these novel cocrystals of ZLP were determined in a phosphate buffer solution (PBS7) at pH 7. All of these novel cocrystals are more hydrophilic and found to demonstrate enhanced solubility and IDR by up to 18.7 and 4.4 times, respectively.