Development of near zero-order release PLGA-based microspheres of a novel antipsychotic

Publication date: 10 January 2017 Source:International Journal of Pharmaceutics, Volume 516, Issues 1–2 Author(s): Jinlong Zhao, Lexi Wang, Chunyu Fan, Kongtong Yu, Ximing Liu, Xiaolei Zhao, Dan Wang, Wenhua Liu, Zhengxing Su, Fengying Sun, Youxin Li The novel antipsychotic isoperidone, a prodrug of paliperidone, was designed to improve liposolubility for the development of poly(D,L-lactide-co-glycolide) (PLGA)-based microspheres to achieve near zero-order release behaviour in vivo. Microspheres with a smooth surface were obtained using the oil-in-water emulsion solvent evaporation method and yielded a high encapsulation efficiency of 92%. Pharmacokinetic studies in beagle dogs showed a one-week plateau phase followed by a two-week quasi-zero-order release with no burst release. The in vitro release method with a good in vitro-in vivo correlation was also established. Pharmacodynamic evaluation was performed using the MK-801-induced schizophrenic behavioural mouse model, and the sustained suppressive effect lasted two weeks. The pharmacokinetic-pharmacodynamic (PK-PD) relationship of isoperidone microspheres was compared to that of oral administration of free drug. The results revealed a strong correlation between the plasma drug level and the antipsychotic effect. A stable drug plasma concentration was detected in mice both intraday and interday from 8 to 22 d after a single injection of isoperidone microspheres, and a sustained suppressive effect on the schiz...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research