Abstract
The degree of cross-linking of albumin microspheres, with and without drug, was assessed using turbidity measurements carried out in the presence of water and the protein denaturant guanidine hydrochloride (GuHCl) at a concentration that disrupted noncovalent bonds while having no effect on covalent bonds. The measurements allowed calculation of a turbidity ratio (T G/T W), expressed as the ratio of the turbidity of albumin microspheres in 6 M GuHCl (T G) divided by that in water (T w). A linear relation existed between T G/T W and the (i) temperature at which the microspheres were prepared, (ii) concentration of the cross-linking agent glutaraldehyde, and (iii) time of exposure to a second cross-linking agent, formaldehyde vapor, three conditions that increase the degree of cross-linking. The turbidity ratio also increased as the concentration of the albumin solution used to prepare the microspheres increased from 25 to 50%. Drug release from the microspheres consisted of an initial, rapid, burst followed by a second, slower, phase. The rates in both release phases were inversely related to the turbidity ratio, suggesting that this parameter has utility as an indicator of the degree of cross-linking in albumin microspheres.
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Rubino, O.P., Kowalsky, R. & Swarbrick, J. Albumin Microspheres as a Drug Delivery System: Relation Among Turbidity Ratio, Degree of Cross-linking, and Drug Release. Pharm Res 10, 1059–1065 (1993). https://doi.org/10.1023/A:1018979126326
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DOI: https://doi.org/10.1023/A:1018979126326