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

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.

Nano-coating of β-galactosidase onto the Surface of Lactose by Using an Ultrasound-assisted Technique

“…In addition, foaming of the protein solution during nebulization might provoke unfolding of their native structure and the aggregation of macromolecules, with a subsequent loss of activity (15). Atomized droplets possess a large airliquid interface that might also affect protein stability (16)(17)(18).…”

Statistical Modeling of protein spray drying at the lab scale

“…Even so, a growing number of studies have confirmed the promise of spray drying to produce dried biopharmaceuticals [2][3][4][5][6]. Some advantages of spray drying include the ability to produce a dry powder rapidly (eg, compared to lyophilization) and the ability to control the particle size distribution.…”

Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug

“…There was no obvious correlation between the measured yield and the different conditions. However, the yield values in wt% obtained are comparable to or slightly higher than other liquid atomization techniques such as spray drying and ultrasonic atomization [54,57,58]. The entrapment efficiencies of CEL in the particles were found to be in the range 88 -99%.…”