High Solubility Crystalline Pharmaceutical Forms of Blonanserin

Blonanserin (BLN) is an antipsychotic drug having poor aqueous solubility. In continuation of our preliminary work ( CrystEngComm 2012, 14, 2367−2372), the aim of this study was to improve physicochemical properties of the drug, such as solubility, dissolution rate, and stability. Novel crystalline forms of BLN were obtained by liquid-assisted grinding with pharmaceutically acceptable coformers such as succinic acid (SUC), suberic acid (SBA), nicotinic acid (NIA), methanesulfonic acid (MSA), and toluenesulfonic acid (TsOH). Four salts of blonanerin [BLNH + –SUC – (1:1), BLNH + –NIA – (1:1), BLNH + –TsO – (1:1), and BLNH + –MSA – (1:1)], a salt hydrate BLNH + –MSA – –H 2 O (1:1:1), and a cocrystal BLN–SBA (1:0.5) are reported in this paper. All multicomponent phases were characterized by IR, Raman, and 13 C ss-NMR spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), and their structures were confirmed by single crystal X-ray diffraction. The crystal structures are sustained by ionic N + –H···O – H-bonds except in the BLN–SBA cocrystal, which has a neutral COOH···N(tertiary amine) H-bond. These novel salts exhibited a faster intrinsic dissolution rate (IDR) compared to the parent drug BLN, and they exhibited good stability (2 months) under accelerated ICH conditions of 75% RH at 40 °C, except BLN + –MSA – anhydrate. The BLNH + –MSA – –H 2 O salt hydrate exhibited the highest solubility (464 times) and dissolution rate (126 times) in 60% EtOH–water medium together with good stability.