Formulation and in vivo pharmacokinetic studies of iloperidone depot injection

Abstract

Iloperidone is a new antipsychotic agent having good tolerability and side-effects profile with respect to long term drug administration. Presently, it is only available as tablet dosage forms of 1-12 mg strengths for twice a day administration. This article reports the pharmacokinetic studies of a novel in situ depot injection formulation of iloperidone developed for once a month administration. The formulation is based on the use of sucrose acetate isobutyrate as a gelling agent for depot formation in situ. It is simple to prepare, possesses an acceptable syringeability and exhibits a controlled and consistent zero order drug release in vitro for one month. The in vivo pharmacokinetic studies performed in male albino Wistar rats for one month showed a mean peak plasma drug concentration of 871.8 ng/mL in 3 days, a mean residence time of 28.9 days, the terminal half-life of 24 days, and a terminal elimination rate-constant of 0.0289/day. The plasma concentration profile of the developed formulation demonstrated a persistent plasma level of iloperidone for one month without any significant burst release and with a good in vitro ñ in vivo correlation.