Protective Effect of Sucrose on Spray Drying of Oxyhemoglobin

Labrude, Pierre; Rasolomanana, M.; Vigneron, C.; Thirion, Christian; Chaillot, Bernard

doi:10.1002/jps.2600780311

Cited by 68 publications

(33 citation statements)

References 21 publications

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“…23 In an early study 3 it was found that those carriers which gave the best protein process stability also gave the best storage stability. The effect on T inlet /T outlet on the balance between process and storage stability has, however, not yet been clarified.…”

Section: Figure 5sprocessmentioning

confidence: 98%

“…Sucrose (0.25 M), for example, reduced the formation of methemoglobin on spray-drying hemoglobin at an inlet air-temperature of 100°C from 50% to <4%. 3 Trehalose, arginine, and sucrose completely ameliorated the activity loss of spray-dried -galactosidase. 4 Both trehalose and sucrose have, however, been reported to be difficult to spray-dry, at least in the placebo state.…”

Section: Introductionmentioning

confidence: 98%

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Stability and surface activity of lactate dehydrogenase in spray‐dried trehalose

Adler

Lee

1999

Journal of Pharmaceutical Sciences

131

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The stability of the model protein lactate dehydrogenase (LDH) during spray-drying and also on subsequent dry storage was examined. Trehalose was used as a carrier. The spray-drying temperatures Tinlet and Toutlet have a measurable effect on LDH inactivation. Low Tinlet produced the least process inactivation, but gave a high residual moisture content making the protein's storage stability poor. High Tinlet reduced residual moisture and improved storage stability, but at the cost of high process inactivation. As already found for other systems, addition of a surfactant (in this case polysorbate 80) could ameliorate process inactivation of LDH at Tinlet = 150 degreesC. Surfactant had, however, a deleterious effect on storage stability of LDH, the vital factor being the molar ratio of surfactant/protein in the dried product. By using electron spectroscopy it was shown that LDH has a 10 times higher surface concentration in the dried trehalose particles than expected for a homogeneous distribution. Surface tension measurements at the water/air interface proved that LDH is surface active, although the Gibbs equation appeared to be inapplicable. Calculations of spray-droplet formation time and drying time indicate than the extent of diffusion-driven LDH adsorption to the liquid/air interface is sufficient to account for the measured amount of LDH inactivation during spray-drying. The presence of 0.1% polysorbate 80 to the spray solution prevents LDH from appearing at the surface of the dried particles. As a negative control, the phosphatide Lipoid E 80 does not prevent the appearance of LDH in the surface according to electron spectroscopy and does not therefore prevent LDH inactivation during spray-drying at Tinlet = 150 degreesC.

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Section: Figure 5sprocessmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

Stability and surface activity of lactate dehydrogenase in spray‐dried trehalose

Adler

Lee

1999

Journal of Pharmaceutical Sciences

131

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“…Bound water molecules are essential to preserve the native conformation of DNA and protein vaccines. As bound water is removed by the lyophilization step, a compound that functions in the same manner as the water must be introduced in order to maintain the integrity of the DNA or protein [50]. Therefore, the active pharmaceutical ingredient is homogeneously dispersed within the excipient matrix of the lyophilized microparticle.…”

Section: Sfd Of Particles For Powder Injectionmentioning

confidence: 99%

“…Beyond these requirements, some other characteristics of fundamental importance must be taken into account, such as drug tolerance to moisture, requirement for buffers, and sugars that stabilize biomolecules by replacing water of their solvation sphere. Biopharmaceutical drugs may need other additives such as cryoprotectants [50,53], process shear protectants, antioxidants, densifiers, and binders to manufacture appropriate particles or additives to improve the properties of the particles for power injection. Bioerodible carriers, slowly dissolving excipients, or specific less soluble salts may provide sustained release and altered pharmacokinetics to improve drug performance [22].…”

Section: General Requirementsmentioning

confidence: 99%

Needle-Free Delivery of Powdered Protein Vaccines: A New and Rapidly Developing Technique

Ziegler

2008

J Pharm Innov

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“…The addition of solutes is used for producing marketable finished protein products, e.g. in spray drying, where solutes are required to protect the protein during the drying process (Luyben et al, 1982;Labrude et al, 1989). To enhance an enzyme's thermostability, the inactivation rate constants need to be decreased and the activation energy shifted to higher values (Weng et al, 1991;De Cordt et al, 1994).…”

Section: Introductionmentioning

confidence: 99%