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5939515 
Journal Article 
Albumin microspheres as a drug delivery system: relation among turbidity ratio, degree of cross-linking, and drug release 
Rubino, OP; Kowalsky, R; Swarbrick, J 
1993 
1 
Pharmaceutical Research
ISSN: 0724-8741
EISSN: 1573-904X 
10 
7 
1059-1065 
English 
8378248 
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 (TG/TW), expressed as the ratio of the turbidity of albumin microspheres in 6 M GuHCl (TG) divided by that in water (TW). A linear relation existed between TG/TW 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.