Format

Send to

Choose Destination
Int J Pharm. 2017 Feb 25;518(1-2):335-341. doi: 10.1016/j.ijpharm.2016.12.059. Epub 2016 Dec 30.

Charge-assisted bond N+H mediates the gelation of amorphous lurasidone hydrochloride during dissolution.

Author information

1
School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China.
2
School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
3
School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: amicute@163.com.
4
School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: weiyuanfengyuer@yeah.net.

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.

KEYWORDS:

Amorphous; Charge-assisted bond; Gelation; Lurasidone hydrochloride

PMID:
28043915
DOI:
10.1016/j.ijpharm.2016.12.059
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center