期刊
PHARMACEUTICAL RESEARCH
卷 17, 期 7, 页码 863-870出版社
KLUWER ACADEMIC/PLENUM PUBL
DOI: 10.1023/A:1007568511399
关键词
protein; spray-dry; surfactant; surface-composition; ESCA
Purpose. To characterize via electron spectroscopy for chemical analysis (ESCA) the surface of spray-dried particles of trehalose plus a protein (bovine serum albumin). Additionally, to show how and why the addition of a surfactant reduces protein adsorption, and by this mechanism could reduce protein instability during spray-drying. Methods. Aqueous solutions of trehalose plus bovine serum albumin (bSA) were spray-dried with increasing concentrations of surfactant. The surface composition of the dried particles was examined using ESCA. Results. The presence of bSA, trehalose, and surfactant could be detected quantitatively in the particle surface. In the absence of surfactant the bSA had a large surface excess concentration (determined via its N atoms). Increasing concentration of polysorbate 80 reduced the surface excess of bSA in a concentration-dependent manner. At high polysorbate 80 concentration (5 mg/ml) the bSA could no longer be detected in solid surface. Using sodium dodecyl sulfate it was shown that the reduction in surface concentration of the protein is accompanied by a simultaneous increase in surface concentration of the surfactant. Neither surfactant fully covers the surface at the point of complete protein exclusion. Conclusions. ESCA provides a direct, quantitative measure of the surface composition of spray-dried trehalose/protein/surfactant particles. Surfactant reduces protein adsorption at the water/air-interface. This appears to be a result of complex formation with the surfactant within the bulk spray solution.
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