Farshad Ramazani, Senior Expert Science & Technology, Novartis gave an overview of the advantages of long acting injectables (LAIs) over traditional medications, the main ones being improved patient adherence and diminished drug level fluctuations. Ramazani advocated for using the past to shape the future of long-acting injectables.
Drugs can be physically or molecularly dispersed in the polymer matrix in the form of microparticles, implants or in situ forming gel that can be administered in the patient and the drug can be released from its depot in a prolonged manner. Nowadays engineering a drug substance itself requires making it more hydrophobic and designing particle size are the essentials for making a long acting injectable.
Ramazani outlined the use of PLGA polymers in LAIs. PGLA is a co-polymer of glycolic and lactic acid. It is biodegradable, biocompatible and commercially available with many different compositions. The most common preparation for PLGA microparticles are emulsion solvent evaporation techniques.
This approach requires dissolving the drug and polymers together in an organic solvent and emulsified in a water phase to form droplets. As the solvent evaporates, solid particles form encapsulating the drug, which are then washed, sterilised, and can be filled into vials or syringes for administration.
Ramazani presented Sandostatin LAR and Signifor as examples of marketed LAI products. Sandostatin is primarily used for long-term treatment of severe diarrhoea and flushing episodes associated with metastatic carcinoid tumours. Signifor is used for the treatment of Cushing's disease when surgery is not an option or has failed.
Moving on to the challenges, there are several associated with manufacturing including the need for scalable processes, robust analytical tools, and suitable sterilisation methods. Terminal sterilisation techniques such as gamma irradiation were noted, though some formulations require aseptic manufacturing due to stability concerns.
He also added that the lack of standardised guidelines contributes to the complexity of LAI development. Ramazani wrapped up his talk by advocating for a patient-centric approach, particularly favouring subcutaneous administration.
