Formulation development and pharmacokinetic studies of long acting in situ depot injection of risperidone

Vineet Dubey,Tulsi Ram Saini

doi:10.1590/s2175-97902022e18809

Abstract

Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.

Highlights

The psychological attitude of schizophrenic patients is generally negative and reluctant towards the drug therapy and, their long term treatment through oral drug therapy is always associated with poor patient compliance and non-adherence to drug administration and dosing schedule (Kane, Kishimoto, Correll, 2013)
Risperidone was supplied by M/S RPG Life Sciences Ltd., Mumbai, India, sucrose acetate isobutyrate by M/S Eastman Chemical Company, Kingsport, USA, and polycaprolactone by Piramal Healthcare, Mumbai, as gift samples
Particle size: The d10, d50, and d90 values of risperidone drug powder used in the formulation were 6.422, 16.396, and 31.593 μm, respectively with a polydispersity index of 1.535

Summary

Introduction

The psychological attitude of schizophrenic patients is generally negative and reluctant towards the drug therapy and, their long term treatment through oral drug therapy is always associated with poor patient compliance and non-adherence to drug administration and dosing schedule (Kane, Kishimoto, Correll, 2013). Valenstein et al (2006) have reported that around 61% psychotic patients did not observe strict medication schedule in their four year study at some point of time during drug therapy with 18% patients being consistently poor in their dosage administration adherence and rest 43% showing. Administration of drug in the form of long acting depot injection eliminates the direct involvement of patients in drug administration and effectively overcomes the above problem of patient non-compliance which is otherwise inevitable in the oral drug therapy (Kaplan, Casoy, Zummo, 2013).

Objectives

Methods

Results

Conclusion