Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies

摘要

The objective of this study was to develop a novel implant containing risperidone intended for long-term treatment in Schizophrenia utilizing in vitro in vivo correlation (IVIVC) studies. Different implants (F1-F8) containing an antipsychotic drug, risperidone, were prepared using a hot melt extrusion technique by taking polycaprolactones of different molecular weights (Mwt. 15000, 45000, 80000) either alone or as their blends, and PLGA (75:25). The implants contained 40% of the drug. After fabrication, the implants were characterized for various in vitro properties such as drug release and physical strength. Prior to conducting drug release studies, optimum drug release method was developed based on IVIVC studies. An optimized formulation based on drug release and physical strength at the end of fabrication was selected from the various implants fabricated. The bioactivity, reversibility, and IVIVC of optimized formulation were determined using pharmacokinetic studies in rats. Short-term stability studies were conducted with optimized formulation. Drug release depended on polymer molecular weight. Implant fabricated using 50:50 polycaprolactone 45,000 and polycaprolactone 80,000 was considered optimized implant. Optimized formulation selected released the drug for 3-months in vitro and was physically rigid. The optimized implant was able to release the drug in vivo for a period of 3 months, the implants are reversible throughout the delivery interval and, a 100% IVIVC was achieved with optimized implant, suggesting the development of 3-month drug-releasing implant for risperidone. The optimized implant was stable for 6 months at room temperature (25°C) and 45°C. A novel implant for risperidone was successfully prepared and evaluated.Keywords: Implant, in vitro in vivo correlation, removability, risperidone, schizophrenia, stability