Determination of the internal morphology of poly (D,L-lactide) microspheres using stereological methods

The morphological characteristics of the internal structure of poly (D,L-la ctide) microspheres have been determined by stereological methods in two di fferent formulations of microspheres, with different internal structures, p repared by using a double emulsion method. In one formulation the internal emulsion was produced by homogenisation at 3000 rpm, whilst the other was p repared at 11 000 rpm. As expected the formulation prepared at the lower sp eed contained larger and more broadly distributed pores than that prepared at the higher speed. The porosity, pore size distribution and total interna l surface area of the microspheres were obtained by stereological methods f rom electron microscopic measurements of the sectioned microspheres. It was found that whilst the porosity of the microspheres was 0.6 in both formula tions, the preparation method gave rise to large differences in their pore size distribution characteristics. The pore size distribution was simulated by computer modelling to validate and compare alternative stereological al gorithms. It was found that the Saltykov unfolding method predicts the meas ured pore size distribution more accurately than the Cruz-Orive unfolding m ethod (at significance level alpha=0.1). This finding was attributed to the violation of one of the basic assumptions of the Cruz-Orive unfolding meth od. (C) 1999 Elsevier Science BN. All rights reserved.