Feasibility study on spray-drying protein pharmaceuticals: recombinant human growth hormone and tissue-type plasminogen activator.
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 degrees C) as the drying medium, hGH could be dried to a residual moisture content of < or = 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.
Mumenthaler
M
M
Department of Pharmaceutical Research and Development, Genentech Inc., South San Francisco, California 94080.
Hsu
C C
CC
Pearlman
R
R
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004229:Dithiothreitol; D013006:Growth Hormone / Q000737:chemistry*; D006801:Humans; D006813:Humidity; D010084:Oxidation-Reduction; D011136:Polysorbates; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D010959:Tissue Plasminogen Activator / Q000737:chemistry*
D011136:Polysorbates; D011994:Recombinant Proteins; D013006:Growth Hormone; D010959:Tissue Plasminogen Activator; D004229:Dithiothreitol