Sodium Hydroxide → Ibandronate Sodium Anhydrous

Participants

Reaction Steps

A solution of sodium hydroxide (0.63 g) in water:ethanol (40:60 v/v, 12 ml) was added dropwise to a solution of amorphous ibandronic acid (5 g) in water:ethanol (40:60 v/v, 71 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for an additional 3.5 hours to obtain a pH of 4.03. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was filtered, washed with ethanol (2×25 ml), and dried in a vacuum oven at 50° C. for 18 hours to give 4.9 g of ibandronate sodium crystal form S. Form S can exhibit a weight loss of about 11% to about 12%, or less in TGA.

Provenance & Evidence