A new concept for interpretation of first-order release from albumin microspheres.
A release mechanism from a microsphere that consisted of a water-swellable polymer and a uniformly dispersed, relatively small number of very slightly soluble large-core particles was considered. When the microsphere is dipped in release media the polymer swells instantly, and every core particle dissolves in the release media in the space between the core particles and the swollen polymer to make a saturated solution. It is assumed that Fickian diffusion of dissolved core substance between all spaces filled with saturated solution and outer sink occurs independent of each other, and release from one entire microsphere is the sum of diffusion from all spaces in the microsphere. Then, derived theoretical release kinetics is found to be first-order, and the derived first-order release rate constant is expressed as a function of the following parameters: radius of core particle, radius of the microsphere, solubility of core substance to media solution, density of the core particle, and permeability constant of core substance in swollen polymer. When rate constants were measured from release tests, varying each parameter, the relation between constants and each parameter follows the function. The permeability constant, which was calculated applying the function on measured rate constants and other known parameters, was in good agreement with the permeability constant measured from permeation study of planar membrane prepared in similar conditions to when preparing microspheres. These results are thought to show the validity of the mechanism and function proposed.
Okada
J
J
Product Development Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Asano
S
S
Kondo
T
T
D002225:Carbazilquinone / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000737:chemistry*; D007700:Kinetics; D008863:Microspheres; D008956:Models, Chemical; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013416:Sulfamerazine / Q000008:administration & dosage
D003692:Delayed-Action Preparations; D002225:Carbazilquinone; D012710:Serum Albumin, Bovine; D013416:Sulfamerazine