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 degreesC. 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 buf fer was considered the most promising stabilizer for minodronic acid, the p H-stability relationship in 100 mM citrate with pH ranging from 3 to 7 was evaluated during storage for 4 weeks at 60 degreesC. The results demonstrat e that solution pH of 3-5 result in optimal stability of minodronic acid wi th no formation of precipitates. A while precipitate was observed in citrat e-containing sample solutions with pH of 6 and 7. Analysis of the isolated precipitate provided support for the hypothesis that the precipitate is a c omplex between minodronic acid and aluminum ions apparently leached from th e glass of the ampoules. (C) 2001 Elsevier Science B.V. All rights reserved .