Development of biodegradable in situ implant and microparticle injectable formulations for sustained delivery of haloperidol

The objective of this study is to formulate injectable, biodegradable sustained release in situ implant (ISI), and in situ microparticle (ISM) formulations of haloperidol. Factors affecting the in vitro drug release, pharmacokinetics, and stability of the formulations were investigated. The concentration of the polymer, poly(lactide-co-glycolide) acid (PLGA), and the type of solvents showed a pronounced effect on the in vitro drug release from the ISI and ISM formulations. The ISM formulation [20% PLGA in N-methyl-2-pyrrolidone (NMP)–peanut oil, 1:4] showed reduced maximum plasma concentration (60 versus 44 ng/mL) and longer release (30 days, plasma concentration of 8 ng/mL versus 20 days, plasma concentration of 6 ng/mL) compared with the ISI formulation (20% PLGA in NMP) after intramuscular injection in rats. The delivery of haloperidol can be extended further by changing the concentration, molecular weight, and lactide-to-glycolide ratio of the PLGA. These formulations can be easily administered by both intramuscular and subcutaneous injections. The shelf lives of both systems were found to be 2 years when stored at 4°C. Haloperidol can be formulated as an injectable ISI or ISM systems suitable for 1 month or longer release. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3753–3762, 2012