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––H2O (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 13C 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––H2O salt hydrate
exhibited the highest solubility (464 times) and dissolution rate
(126 times) in 60% EtOH–water medium together with good stability.