Sodium Hydroxide → Ibandronate Sodium Anhydrous

Participants

Reaction Steps

A solution of sodium hydroxide (0.63 g) in water:acetonitrile (40:60 v/v, 12.33 ml) was added dropwise to a solution of amorphous ibandronic acid (5 g) in water:acetonitrile (40:60 v/v, 71 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for an additional 1 hour to obtain a pH of 4.05. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was isolated by vacuum filtration, washed with acetonitrile (2×20 ml), and dried in a vacuum oven at 50° C. for 20 hours to obtain 3.9 g of ibandronate sodium crystal form Q5. Form Q5 can exhibit a weight loss of about 5% to about 11% in TGA.

Provenance & Evidence