Ammonium Bicarbonate → Ammonia

In 1997, Overcashier et al. (Overcashier D. E. et al., Jour. Pharm. Sci. 86(4):455-459 (1997)) published an article describing the preparation of excipient-free recombinant human tissue-type plasminogen. The article states that precipitation of proteins by pH adjustments (iso-precipitation) or ionic strength regulation often leads to denaturation of the proteins resulting in reduced therapeutic activity. A method based on lyophilization of the protein from the ammonium bicarbonate was described. It was shown that the freeze-drying procedures took place in two steps. A large pressure increase was observed in the procedure when water was removed, and it was suggested that ammonium bicarbonate was evenly distributed over the lyophilization product. The following sublimation of ammonium bicarbonate resulted in a decomposition into water, carbon dioxide and ammonia which gave rise to the mentioned pressure increase. Thus, in the presence of ammonium bicarbonate it can be technically difficult to perform the freeze-drying procedure which might give reproducibility problems for the solid bulk material.

1. customthe preparation of excipient-free recombinant human tissue-type plasminogen
2. customThe article states that precipitation of proteins by pH adjustments (iso-precipitation) or ionic strength regulation
3. customresulting in reduced therapeutic activity
4. temperatureA large pressure increase
5. customwas removed

ORD record

ord-c22d57bfc00140cd96fc227f81256de3

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06566329B1