Sustained Release In-situ Forming Liquid Crystal Gel Containing Risperidone: In-vitro Evaluation and Pharmacokinetics in Rabbits

Abstract

Introduction: The present study aimed to extend a novel vehicle for sustained delivery of risperidone to improve schizophrenia therapy. Risperidone is used as an anti-psychotic drug to treat various psychological conditions. Lipid liquid crystal (LLC) gel containing various lipids, solvents, and stabilizers turns into a sustain-release gel in contact with the aqueous medium. Method: Glycerol monooleate (GMO), glycerol dioleate (GDO), and glycerol trioleate (GTO) alongside several ratios of phosphatidylcholine (PC) to oil and N-methyl-2-pyrrolidone (NMP) solvent percent (w/w %) were assessed for initial burst release (IBR) for LLC. Some In-vitro evaluations, pharmacokinetics assessments, and histopathological studies were done to gain optimal formulation. Results: the GDO-based LLC showed lower IBR in comparison to other glycerol-based formulations. Pharmacokinetic data revealed that GDO at PC:oil = 2.2:1 and NMP = 30% made a sustained release for two months. Risperdal CONSTA® can reach the required therapeutic levels after 2–3 weeks; however, over the lag period, co-administration of oral risperidone is essential. The histopathology results indicated approximately no side effects in rabbits. Conclusion: This study confirms the great potential of GDO-based LLC in comparison to Risperdal CONSTA®. Furthermore, the results showed that a single injection of GDO-based formulations could maintain drug release in both in-vitro and in-vivo for two months in the therapeutic range.