Phosphoric Acid → Pamidronate Disodium Anhydrous

Participants

Reaction Steps

For a batch size of 5 L, 587.5 g (3.2 moles) of mannitol is dissolved in 3.5 L of water. Pamidronic acid (31.6 g, 0.133 moles) is mixed with a 1.0 L aliquot of the mannitol solution to form a slurry. The slurry is transferred into the remainder of the mannitol solution, and stirred for about 15 min. Aqueous 1 N sodium hydroxide (270 ml) is added and the mixture is stirred until a clear, colorless solution results. The pH is adjusted to 6.5±0.1 using either 1 M aqueous phosphoric acid or 1 N aqueous sodium hydroxide, as needed. The solution is filtered through a 0.22 micron filter, and filled at 20° C. into glass vials at 4.0 ml (4.172 g)/vial, and the vials are sealed in the lyophilizer in an inert atmosphere under sterile conditions.

Provenance & Evidence