Development of a novel one-step production system for injectable liposomes under GMP.
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.
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Ryo
R
Araki
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Takashi
T
Matsuzaki
b Department of Pharmacy , Osaka University Hospital , Osaka , Japan.
Ayumi
A
Nakamura
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Daisaku
D
Nakatani
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Shoji
S
Sanada
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Hai Ying
HY
Fu
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Keiji
K
Okuda
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Masaki
M
Yamato
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Shota
S
Tsuchida
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.
Yasushi
Y
Sakata
a Department of Cardiovascular Medicine , Osaka University Graduate School of Medicine , Osaka , Japan.|c Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine , Kagawa University , Kagawa , Japan.
Tetsuo
T
Minamino
D019840:2-Propanol / Q000737:chemistry; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D004867:Equipment Design; D005612:Freeze Drying / Q000379:methods; D007267:Injections; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
D000935:Antifungal Agents; D008081:Liposomes; D016572:Cyclosporine; D019840:2-Propanol
GMP; Liposome; automation; cyclosporine; injectable; one-step