Risperidone Microemulsion for Transnasal Delivery: Pharmacodynamic and Pharmacokinetic Evaluation

Abstract

The present study describes development and evaluation of risperidone (RPD) microemulsions (RME) for transnasal delivery in the treatment of schizophrenia. The RME was prepared by the titration method and characterized for physicochemical parameters. Pharmacodynamic evaluations (apomorphine – induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with 99mTc (technetium) and biodistribution of drug in the brain was studied using Swiss albino rats. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. RME were transparent and stable with mean globule size of 15- 30 nm and zeta potential of -30mV to -40mV. In pharmacodynamic studies, significant (P<0.05) variation in parameters estimated, were found between the treated and control groups. 99mTc-labeled risperidone solution (RS)/RME/RPD mucoadhesive microemulsion (RMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of RMME compared to intravenous RME was found to be 6 to 8 fold higher indicating larger extent of distribution of the drug in brain. Drug targeting efficiency, and direct drug transport were found to be highest for RMME post-intranasal administration compared to intravenous RME. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. This investigation demonstrates a more rapid and larger extent of transport of risperidone into the brain with intranasal RMME, which may prove useful for treatment of schizophrenia. Keywords: Brain scintigraphy, microemulsion, pharmacokinetic study, pharmacodynamic study, risperidone.