In this comprehensive review, we explore the key principles, latest advancements, and emerging trends in the formulation and industrial manufacturing of lipid-based complex injectables. Our goal is to provide valuable insights for researchers and industry professionals in this rapidly evolving field.
Mariana Biscaia-Caleiras, Nuno A. Fonseca, Ana Sofia Lourenço, João Nuno Moreira, Sérgio Simões
Journal of Controlled Release
Volume 373, 2024
https://www.sciencedirect.com/science/article/abs/pii/S0168365924004528?via%3Dihub
Abstract
Lipid-based complex injectables are renowned for their effectiveness in delivering drugs, with many approved products. While significant strides have been made in formulating nanosystems for small molecular weight drugs, a pivotal breakthrough emerged with the recognition of lipid nanoparticles as a promising platform for delivering nucleic acids. This finding has paved the way for tackling long-standing challenges in molecular and delivery aspects (e.g., mRNA stability, intracellular delivery) that have impeded the clinical translation of gene therapy, especially in the realm of immunotherapy. Nonetheless, developing and implementing new lipid-based delivery systems pose significant challenges, as industrial manufacturing of these formulations often involves complex, multi-batch processes, giving rise to issues related to scalability, stability, sterility, and regulatory compliance. To overcome these obstacles, embracing the principles of quality-by-design (QbD) is imperative. Furthermore, adopting cutting-edge manufacturing and process analytical tools (PAT) that facilitate the transition from batch to continuous production is essential. Herein, the key milestones and insights derived from the development of currently approved lipid- nanosystems will be explored. Additionally, a comprehensive and critical overview of the latest technologies and regulatory guidelines that underpin the creation of more efficient, scalable, and flexible manufacturing processes for complex lipid-based nanoformulations will be provided.