Evaluation of a statistical model for the formation of poly[acryloyl hydroxyethyl starch] microspheres

Purpose. To characterize the network structure of Poly(Acryloyl Hydroxyethyl Starch) (Ac-HES) microspheres and test the theoretical model and the hypothesis that the rate of swelling of microspheres is inversely related to the extent of crosslinking. Methods. Microspheres were prepared with varying degrees of derivatization (DD) and molar ratios (MR) and subjected to the characterization of matrix structure by dynamic and equlilibrium swelling studies utilizing direct microscopic observation and the Flory-Rehner equation. The dependence of average molecular weight between crosslinking Mc, on DD and MR were compared to test the validity of the model. Results. Study of the dependence of Mc on the microspheres preparation parameters, DD and MR, showed that at constant MR, the Mc decreased with DD, while at constant DD, the Mc initially decreased with MR to a minimum, and then increased with MR, complying with the model prediction. Dynamic swelling of microspheres showed a monotonical increase to equilibrium size featured by two time variables, Tp and Teq, that were dependent on Mc; this permitted a conceptual view of the general structure of the Ac-HES microspheres. The Mc, which was more accurately determined by the weight method (as opposed to volume method), was independent of the size of microspheres although there was evidence of variation among particles within a batch. Conclusions. The results validated the model in describing the polymerization/crosslinking reaction of the Ac-HES microsphere system and suggested that Mc is the principal factor in controlling release.