ISSN:
1573-904X
Keywords:
spray-drying
;
recombinant methionyl human growth hormone
;
tissue-type plasminogen activator
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The feasibility of spray-drying solutions of recombinant methionyl human growth hormone (hGH) and tissue-type plasminogen activator (t-PA) was investigated. hGH was formulated in a mannitol phosphate buffer and t-PA was used in an arginine phosphate formulation containing 0.004% (w/v) polysorbate 80. Using filtered air (90 – 150°C) as the drying medium, hGH could be dried to a residual moisture content of ≤4%. However, approximately 25% of the protein was degraded during the processing. Results of atomization studies suggest that surface denaturation at the air–liquid interface of the droplets in the spray plays a major role in the degradation of the protein. The addition of 0.1% (w/v) polysorbate 20 into the hGH formulation reduced the formation of soluble and insoluble aggregates by approximately 90% during atomization. During spray-drying the addition of 0.1% (w/v) polysorbate 20 reduced the formation of soluble and insoluble aggregates by approximately 70 and 85%, respectively. In contrast, t-PA remained intact upon atomization. Depending on the spray-drying conditions, product powders with a residual moisture content between 5 and 8% were obtained. No oxidation, aggregation, or denaturation occurred in the protein under several operation conditions. Overall, this study demonstrates that it is feasible to spray-dry t-PA in the current marketed formulation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018929224005
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