Long-acting injectable formulation technologies: challenges and opportunities for the delivery of fragile molecules

• Published in: Expert opinion on drug delivery Vol. 19; no. 8; pp. 927 - 944
• Main Authors: Gonella, Andrea, Grizot, Sylvestre, Liu, Fang, López Noriega, Adolfo, Richard, Joël
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 03.08.2022
• Subjects: Drug delivery; formulation development; long-acting injectables; peptides; proteins
• ISSN: 1742-5247; 1744-7593
• DOI: 10.1080/17425247.2022.2105318

The development of long-acting injectables (LAIs) for protein and peptide therapeutics has been a key challenge over the last 20 years. If these molecules offer advantages due to their high specificity and selectivity, their controlled release may confer several additional benefits in terms of extended half-life, local delivery, and patient compliance. This manuscript aims to give an overview of peptide and protein-based LAIs from an industrial perspective, describing both approved and promising technologies (with exceptions of protein engineering strategies and devices), their advantages and potential improvements to aid their access to the market. Many LAIs have been developed for peptides, with formulations on the market for several decades. On the contrary, LAIs for proteins are still far from the market and issues related to manufacturing and sterilization of these products still need to be overcome. In situ forming depots (ISFDs), whose simple manufacturing conditions and easy administration procedures (without reconstitution) are strong advantages, appear as one of the most promising technologies for the delivery of these molecules. In this regard, the approval of ELIGARD® in the early 2000ʹs (which still requires a complex reconstitution process), paved the way for the development of second-generation, ready-to-use ISFD technologies like BEPO® and FluidCrystal®.