SPRAY-DRYING OF AIR-LIQUID INTERFACE SENSITIVE RECOMBINANT HUMAN GROWTH-HORMONE

Spray-drying is an attractive method for preparing fine recombinant hu man growth hormone (rhGH) powders ii the detrimental effect of protein degradation at the air-liquid interface on the protein can be minimiz ed. In this study, we demonstrated that rhGH degradation (insoluble an d soluble aggregate formation), as the consequence oi air-liquid inter facial degradation, could be prevented using the appropriate formulati on. Adding polysorbate-20 surfactant into the liquid feed (with no pre sence of sugar protectant) significantly reduced the formation of inso luble protein aggregates, while adding the divalent metal zinc ion eff ectively suppressed the formation oi soluble protein aggregates. The c ombination of the two yielded a spray-dried rhGH powder having insigni ficant protein degradation. Our data suggest that the two components m ight protect the protein through different mechanisms. Polysorbate mol ecules occupy the air-liquid interlace of spray droplets, thereby redu cing the chance for rhGH to form insoluble aggregates by surface denat uration. Two zinc ions associate with two rhGH molecules to form a dim er complex that can resist the formation of soluble protein aggregates . Characterization of spray-dried powders by scanning electron microsc opy suggests that both formulation and drying conditions have a strong influence on particle morphology and shape. Overall, spherical rhGH p owders of smooth surface and good biochemical quality can be prepared by spray-drying using this formulation with no addition of sugar prote ctant.