Development of an oil suspension containing granisetron hydrochloride as a sustained-release parenteral formulation for enhancement of pharmacokinetic properties

Abstract

A sustained-release parenteral formulation of granisetron hydrochloride, a water-soluble drug, was developed in the form of an oil suspension loaded with microparticles. Spray drying technique was employed to prepare microparticles of polymers and the drug without using organic solvents. The effects of polymers and oils on the drug release were evaluated. Methylcellulose was found to be the most effective among various polymers examined for the drug sustained-release. Physicochemical characterization suggested that methylcellulose and granisetron hydrochloride interacted within the microparticles via hydrogen bonds and that the drug was transformed to an amorphous state. The optimum sustained-release parenteral formulation was the suspension of the spray-dried microparticles of methylcellulose and granisetron hydrochloride (ratio 5:1) in the mixture of medium-chain triglycerides and castor oil (40:60, V/V). In vitro release study showed the sustained-release characteristics of the optimized formulation up to 72 h. The results of pharmacokinetic studies in rats showed the sustained-release characteristic of the optimized formulation with an extended T-max and the enhanced systemic exposure compared to the drug solution. Encapsulation of hydrophilic drugs with methylcellulose into microparticles combined with the preparation of oil suspensions is a promising approach for the development of sustained-release parenteral formulations.