Albumin microspheres as a drug delivery system: relation among turbidity ratio, degree of cross-linking, and drug release.
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.
Rubino
O P
OP
Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Kowalsky
R
R
Swarbrick
J
J
D000418:Albumins / Q000737:chemistry*; D000584:Amiloride / Q000008:administration & dosage / Q000737:chemistry; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005557:Formaldehyde / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D008863:Microspheres; D009391:Nephelometry and Turbidimetry; D013696:Temperature
D000418:Albumins; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005557:Formaldehyde; D000584:Amiloride; D005976:Glutaral