Solvent-exchange-based in situ forming implants: advances and challenges as long-lasting formulations

INTRODUCTION: In situ forming implants (ISFIs) are long-acting drug delivery systems that solidify at the injection site, creating a depot for sustained drug release from days to months. Compared with preformed implants, ISFIs offer unique advantages, including easier and more convenient administration and simpler manufacturing. Among the different types, solvent-based ISFIs are the most extensively studied and developed formulations. AREAS COVERED: This review analyses advances in solvent-based ISFIs at both preclinical and clinical levels, with emphasis on formulation strategies and therapeutic applications. A literature search was conducted using PubMed and WOS. EMA and FDA databases were also consulted. EXPERT OPINION: Solvent-based ISFIs represent an important strategy for achieving long-lasting effects with a single administration independent of patient compliance. Their main impact has been in mental and substance use disorders, but they are also useful for local effects. To date, one formulation has been approved for periodontitis, though applications in ocular diseases and osteoarthritis are anticipated. A key formulation challenge is to reduce the initial drug release. Most marketed formulations are based on PLGA/PLA dissolved in NMP. Recently, DMSO and PEGylated-based-ISFIs have been approved, which generally provide better drug release control and will likely lead to the development of new formulations.