title: Charge-assisted bond N+H mediates the gelation of amorphous lurasidone hydrochloride during dissolution.
abstract: Lurasidone hydrochloride (LH), the hydrochloride form of lurasidone with a charge-assisted bond N+H, is an atypical antipsychotropic agent for the treatment of schizophrenia. As a BCS class II drug, LH has a low oral bioavailability mainly due to its poor water solubility and low dissolution. In order to improve its solubility, amorphization of LH was performed and characterized. Unexpectedly, the dissolution rate of amorphous LH was much lower than that of crystalline LH. In addition, the amorphous LH powders quickly aggregated when contacting the dissolution media (water, 37°C), and formed a sticky gel adhering on the paddle. The follow-up polarized light microscope, XRPD, DSC, and FTIR analysis found that amorphous LH transformed to crystalline LH during dissolution. On the other hand, no such gelation phenomenon of amorphous lurasidone was observed under the same dissolution condition. However, the gel would reform when dropping concentrated hydrochloric acid slowly into the bottom of the medium during the dissolution of amorphous lurasidone, and XRPD/DSC/FTIR results indicated that the regenerated gel was consisted of crystalline LH, suggesting that the charge-assisted bond N+H in the structure of LH mediated the gel formation of amorphous LH during its dissolution process.
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Qian
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Ma
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Liang
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: amicute@163.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: weiyuanfengyuer@yeah.net.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Wei
mesh_terms: D014150:Antipsychotic Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D005782:Gels; D000069056:Lurasidone Hydrochloride / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D014150:Antipsychotic Agents; D005782:Gels; D000069056:Lurasidone Hydrochloride
keywords: Amorphous; Charge-assisted bond; Gelation; Lurasidone hydrochloride