Mannitol → Bendamustine Mannitol

Participants

Reaction Steps

Two batches (Batch 1 and Batch2) each one with a different pharmaceutical composition comprising solid dispersions in the form of dry powder and substantially free of hydrolysis degradants were produced. For each batch, two pre-drying intermediate compositions were formulated in separate containers. For Batch 1, the aqueous pre-drying composition was formulated consisting of 2380 mg of mannitol dissolved in 70 ml of water. The non-aqueous pre-drying composition was formulated by dissolving 1400 mg of bendamustine in 70 ml of n-propanol. For Batch 2, the aqueous pre-drying composition consisted of 1190 mg of mannitol dissolved in 70 ml of water. The non-aqueous pre-drying composition was formulated by dissolving 700 mg of bendamustine hydrochloride in 70 ml of ethanol. The ethanol/bendamustine solution could be cooled to minimize the extent of possible side reactions. Both feed pumps (see FIG. 10) were set in such a way that the ratio of excipient to API was 1.8 for Batch 1 and 1.9 for Batch 2. Tables 2 and 3 show the process parameters for Batch 1 and Batch 2.

Provenance & Evidence