2003 Volume 63 Issue 2 Pages 65-70
Minodronic acid, a new bisphosphonate, is susceptible to low levels of aluminum ions leaching from regular glass ampoules when in solution. This could lead to an increase in microscopic particles depending on the containers, formulations or storage conditions used. In this study, the compatibilities of three chemically-treated glass ampoules for minodronic acid solution were examined. The formulation that demonstrated a sudden particulate increase in regular glass ampoules after storage for 5 mo at 25°C was used as a test solution. The particulate generation in each ampoule was evaluated by a newly introduced stress test (4 freeze-thaw cycles after storage for 4 wk at 80°C) and a regular long-term test (storage for 6 mo at 25°C). The long-term test revealed that sulfur-treated ampoules and nitric acid-treated ampoules did not show the particulate increase even though silicone-treated ampoules did. In contrast, the stress test, which was designed to quickly choose robust formulations in regular glass ampoules, was inappropriate for choosing suitable ampoules because the results of the stress test did not correlate well with those of the long-term test due to the intense stress placed on the ampoules. SiO2-treated ampoules, which suppressed the particulate increase at 25°C, also generated an excess amount of particles after the stress test. It appears that the protective SiO2 layer was severely damaged due to the harsh temperature conditions.
