Spray-drying of air-liquid interface sensitive recombinant human growth hormone.
J Pharm Sci
; 87(2): 152-9, 1998 Feb.
Article
em En
| MEDLINE
| ID: mdl-9519146
ABSTRACT
Spray-drying is an attractive method for preparing fine recombinant human growth hormone (rhGH) powders if the detrimental effect of protein degradation at the air-liquid interface on the protein can be minimized. In this study, we demonstrated that rhGH degradation (insoluble and soluble aggregate formation), as the consequence of air-liquid interfacial degradation, could be prevented using the appropriate formulation. Adding polysorbate-20 surfactant into the liquid feed (with no presence of sugar protectant) significantly reduced the formation of insoluble protein aggregates, while adding the divalent metal zinc ion effectively suppressed the formation of soluble protein aggregates. The combination of the two yielded a spray-dried rhGH powder having insignificant protein degradation. Our data suggest that the two components might protect the protein through different mechanisms. Polysorbate molecules occupy the air-liquid interface of spray droplets, thereby reducing the chance for rhGH to form insoluble aggregates by surface denaturation. Two zinc ions associate with two rhGH molecules to form a dimer complex that can resist the formation of soluble protein aggregates. Characterization of spray-dried powders by scanning electron microscopy suggests that both formulation and drying conditions have a strong influence on particle morphology and shape. Overall, spherical rhGH powders of smooth surface and good biochemical quality can be prepared by spray-drying using this formulation with no addition of sugar protectant.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônio do Crescimento
/
Química Farmacêutica
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos