Sodium Hydroxide → Ibandronate Sodium Anhydrous

Participants

Reaction Steps

A solution of sodium hydroxide (0.63 g) in water:methanol (60:40 v/v, 19 ml) was added dropwise to a solution of amorphous ibandronic acid (5 g) in water:methanol (60:40 v/v, 106 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for an additional 1.5 hours to obtain a pH of 4.01. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was filtered, washed with methanol (2×25 ml), and dried in a vacuum oven at 50° C. for 19 hours to give 5.2 g of ibandronate sodium crystal form Q3. Form Q3 can exhibit a weight loss of about 7% to about 9% in TGA.

Provenance & Evidence