Stabilization of minodronic acid in aqueous solution for parenteral formulation.
The composition, concentration, and buffer pH of potential minodronic acid formulations were evaluated for their drug stability and for their tendency to generate particles after storage for up to 4 weeks at 60 degrees C. The results indicate that citrate and tartrate buffers maintain drug stability and inhibit the formation of particles. The stability of minodronic acid in these solutions increased slightly as the buffer concentration increased, exhibiting less particle formation than in other buffers. Since citrate buffer was considered the most promising stabilizer for minodronic acid, the pH-stability relationship in 100 mM citrate with pH ranging from 3 to 7 was evaluated during storage for 4 weeks at 60 degrees C. The results demonstrate that solution pH of 3-5 result in optimal stability of minodronic acid with no formation of precipitates. A white precipitate was observed in citrate-containing sample solutions with pH of 6 and 7. Analysis of the isolated precipitate provided support for the hypothesis that the precipitate is a complex between minodronic acid and aluminum ions apparently leached from the glass of the ampoules.
Nakamura
K
K
Novel Pharmaceutical Laboratories, Institute for Drug Development and Research, Yamanouchi Pharmaceutical Co. Ltd., 180 Ozumi Yaizu-shi, 425-0072, Shizuoka-ken, Japan. nakamurk@yamanouchi.co.jp
Tanaka
T
T
Saito
K
K
Yokohama
S
S
Sonobe
T
T
D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004164:Diphosphonates / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry*; D007263:Infusions, Parenteral; D017550:Spectroscopy, Fourier Transform Infrared
D002021:Buffers; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529