Spray-Drying of Air–Liquid Interface Sensitive Recombinant Human Growth Hormone

doi:10.1021/js970308x

Journal of Pharmaceutical Sciences

Volume 87, Issue 2, February 1998, Pages 152-159

https://doi.org/10.1021/js970308x Get rights and content

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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Spray-Drying of Air–Liquid Interface Sensitive Recombinant Human Growth Hormone

Abstract

J. Pharm. Sci.

Biochim. Biophys.

J. Pharm. Sci.

Int. J. Pharm.

The effect of process and formulation variables on the properties of spray-dried β-galactosidase

Pharm. Pharmacol.

The balance between biochemical and physical stability of inhalation protein powders: rhDNase as an example

Spray drying handbook

Drying

Feasibility study on spray-drying protein pharmaceuticals: Recombinant human growth hormone and tissue-type plasminoge activator

Pharmaceutical Res.

Secondary structure considerations during protein spray drying.

Fourier-transform infrared spectroscopy demonstrates that lyophilization alters the secondary structure of recombinant human growth hormone

Pharm. Sci.

Optimization of lyophilization conditions for recombinant human interlukin-2 by dried-state conformational analysis using Fourier-transform infrared spectroscopy

Pharm. Res.

An infrared spectroscopic study of interactions of carbohydrates with dried proteins

Biochemistry

Stabilization of protein structure by sugars

Biochemistry