Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo.

Xieguo Yan,Shiqiang Wang,Kaoxiang Sun

doi:10.3390/pharmaceutics13081210

Abstract

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

Highlights

Schizophrenia is a chronic and severe mental illness that affects more than 20 million people worldwide [1]
The pathogenesis of schizophrenia has yet to be fully characterized; previous studies have reported that certain genes [5] or environmental factors [6] affect the onset of schizophrenia [7,8]
Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil

Summary

Introduction

Schizophrenia is a chronic and severe mental illness that affects more than 20 million people worldwide [1]. It often manifests as syndromes with different symptoms, involving various obstacles in perception, thinking, emotion, behavior, and coordinating mental activities. The course of the disease is usually long with repeated episodes, exacerbations, or deteriorations, and some patients eventually develop degeneration and mental disability [2]. Patients with schizophrenia are 2–3 times more likely to die at an early age than the general population [3]. Long-term medication affects the quality of life of patients, affects family relationships, and leads to drug compliance [4]. The pathogenesis of schizophrenia has yet to be fully characterized; previous studies have reported that certain genes [5] or environmental factors [6] affect the onset of schizophrenia [7,8]

Methods

Results

Conclusion