Product development of AG-331 lyophilized powder for injection.
AG-331, a water-soluble glucuronate salt of a potential anticancer drug, was synthesized using a technology described as "Protein Structure-based Drug Design." A lyophilized product containing 44.4% (w/w) of AG-331, 55.6% (w/w) of mannitol and trace of water was developed for parenteral delivery of AG-331. The pre-lyophilized solution, which contains 2.0% (w/v) of AG-331 and 2.5% (w/v) mannitol can be aseptically filtered through commonly used 0.2-micron filters without significant AG-331 loss. The filter of choice was made of PTFE (polytetrafluoroethylene) membrane. The lyophilized product is stable under accelerated conditions for at least 6 months. The product can be sterilized with gamma-irradiation. The AG-331 reconstituted solution in 5% Dextrose Injection, USP is stable in PVC infusion bags for at least 2 days at 5 degrees C and 30 degrees C.
Chiang
C C
CC
Pharmaceutical Development Department, Agouron Pharmaceuticals, Inc., San Diego, California.
Fessler
D
D
Freebern
K
K
Thirucote
R
R
Tyle
P
P
D015195:Drug Design; D004349:Drug Packaging; D004355:Drug Stability; D005374:Filtration / Q000379:methods; D005612:Freeze Drying / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry*; D013242:Sterilization / Q000379:methods
D007211:Indoles; C087748:AG 331