CHAPTER 5. Development of Risperidone Implant Formulations (DLP-114) for Long-term Maintenance Treatment of Schizophrenia

A subcutaneous implant has been developed to manage the symptoms of schizophrenia for periods of 6–12 months. The implant consists of a titanium cylinder that is filled with a risperidone formulation and capped at one or both ends with a porous polymer membrane. Suitable formulations consist of risperidone (a hydrophobic tertiary amine) blended with acid-generating excipients that convert the drug to a more soluble protonated form upon activation by an aqueous fluid. Under these conditions, the concentration gradient of drug greatly increases across the membranes of the device, and a near-zero-order therapeutic rate of drug release can be achieved through a diffusion-based mechanism. During development, two general classes of risperidone formulations were compared in a key preclinical study, and one was later advanced to clinical trials. Selected results from this study are described herein. It is anticipated that the general implant design and formulation strategies described in this report can be applied to a variety of other existing pharmaceuticals.