Formulation Development and Optimization of Three Month Long-Acting Depot Microspheres for the Treatment of Schizophrenia

Abstract

Schizophrenia, a complex psychiatric disorder characterized by disturbances in thinking, perception, and behaviour, poses significant challenges in treatment adherence. Long-acting injectable (LAI) formulations offer a promising solution, ensuring sustained therapeutic drug levels and improving patient compliance. This project focuses on developing LAI depot microspheres for schizophrenia treatment. Pre-formulation studies of both drug and polymer were conducted, including differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and melting point analysis, along with standard curve establishment for drug assay by high-performance liquid chromatography (HPLC). The drug selected for this purpose belongs to the antipsychotic class, specifically targeting symptoms associated with schizophrenia. Microspheres were chosen to provide sustained release, enhancing therapeutic efficacy and patient adherence, while the solvent extraction method was selected for its efficiency in microsphere preparation. Initially, batches CI001-CI018 were prepared, with CI014 exhibiting a lag phase due to the use of PLA (Resomer 202S). Subsequently, a blend polymer of PLA and PLGA (Resomer 202S + Resomer 502H) was formulated to address this issue. Analytical testing of batch CI017 included DSC, FTIR, particle size analysis, scanning electron microscopy (SEM), assay determination, related substance, residual solvent analysis, and in vitro dissolution studies. CI017 emerged as the preferred batch, demonstrating sustained drug release over three months. Stability data confirmed the product's integrity over one, three, and six months. This project underscores the significance of LAI microspheres in treating schizophrenia, offering sustained drug delivery and improving patient compliance.