Evaluation of the Innovative Drug Delivery Technology Utilized in TV-46000, a Subcutaneous Long-acting Injectable Risperidone Formulation

Abstract: Background TV-46000 is a risperidone extended-release suspension for subcutaneous administration in development for treatment of patients with schizophrenia. TV-46000 is based on an innovative copolymer drug delivery technology licensed from Medincell (Jacou, France). The present report describes evaluation of its copolymer-based drug delivery technology and the extended-release mechanism that enables flexible, interchangeable dosing regimens. Methods The TV-46000 formulation is based on in situ forming technology using biodegradable copolymers dissolved in dimethyl sulfoxide (DMSO). An in vitro depot formation study evaluated the extended release mechanism following subcutaneous administration; measures included testing depot swelling, DMSO release kinetics, changes in copolymer molecular weights, in vitro drug release and depot morphological properties. Results This study confirmed that the formation of the depot is governed by exposure of the drug suspension to the aqueous environment leading to the precipitation of the biodegradable copolymers and solvent exchange process between DMSO and water. Consequently, a biodegradable depot containing risperidone is formed. Risperidone then slowly releases from the depot via a combined mechanism of drug diffusion and gradual copolymer degradation and erosion. The copolymers in TV-46000 are designed to degrade by hydrolysis of the copolymers’ ester bonds and release risperidone over an extended period, allowing for dosing intervals of once monthly or once every two months. Conclusions TV-46000 is a risperidone formulation using an innovative copolymer drug delivery technology that when injected subcutaneously forms a biodegradable depot that releases risperidone over time, and maintains suitable exposure over flexible, once monthly or once every two months dosing intervals.Short Description: TV-46000, a risperidone extended-release suspension for subcutaneous (SC) administration, is based on an innovative copolymer drug delivery technology. An in vitro depot formation study showed that following SC injection of TV-46000, a depot containing risperidone forms due to solvent exchange processes. Risperidone then slowly releases from the depot via drug diffusion and gradual copolymer degradation and erosion, enabling suitable exposure with flexible once monthly or once every two months SC injection dosing regimens.Name of Sponsoring Organization(s): Teva Pharmaceuticals