Development of a novel one-step production system for injectable liposomes under GMP

Abstract

There are few methods available for injectable liposome production under good manufacturing practices (GMP). Injectable liposome production processes under GMP generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. To overcome these limitations, we developed a novel one-step in-line closed liposome production system that integrated all production processes by combining the in-line thermal mixing device with modified counterflow dialysis. To validate the system, we produced liposomal cyclosporine A (Lipo-CsA) and lyophilized the liposomes. The three independent pilot batches were highly reproducible and passed the quality specifications for injectable drugs, demonstrating that this system could be used under GMP. The accelerated stability test suggested that the liposomes would be stable in long-term storage. This one-step system facilitates a fully automated and unattended production of injectable liposomes under GMP.

Keywords:

• Liposome
• GMP
• one-step
• injectable
• automation
• cyclosporine

Acknowledgements

We thank Ms Tomomi Matsuo in the Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan, for her excellent assistance.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This study was supported by a Health Labour Sciences Research Grant from The Ministry of Health Labour and Welfare and the Project Promoting Clinical Trials for Development of New Drugs and Medical Devices from the Japan Agency for Medical Research and Development.