LONG-ACTING INJECTABLES DRUG DELIVERY LINKING RELEASE MECHANISMS, PLATFORM DESIGN AND THERAPEUTIC APPLICATIONS

Long-acting injectables (LAIs) are innovative drug-delivery systems allowing for prolonged controlled release of a drug after a single administration. By decreasing the dosing frequency, long-acting injectable can have a positive impact on treatment compliance, patient convenience, and drug exposure while minimising the peak–trough fluctuations. This review provides an overview of the different formulation approaches used to develop LAIs, including microspheres, Nano crystal suspensions, oil-based depots, in situ forming depots, implants, hydrogels, lyotropic liquid crystalline systems, polymer-lipid hybrids, and modified protein and peptide therapeutics. The review highlights the main advantages and limitations of LAIs, such as patient adherence and consistent drug exposure, while also discussing injection site reactions, prolonged drug exposure, challenges of flexible dose adjustment, manufacturing complexity, and cost. Storage requirements will be discussed. The clinical applications in schizophrenia and bipolar disorder, HIV treatment and prevention, opioid use disorder, growth hormone deficiency, and diabetes. Ophthalmic diseases will be highlighted together with the marketed products in each therapeutic area. Finally, emerging technologies, patient-friendly LAI approaches, biomaterials, artificial intelligence, predictive modelling, and personalised medicine are discussed. In conclusion, LAIs are an important class of drug delivery systems that can have a significant impact on optimal and sustained drug exposure while decreasing the treatment burden on the patient. The complexity of the different formulation approaches and the need for clinical development expertise are still major hurdles that industry is currently trying to address by developing new approaches and manufacturing processes.