Influence of the formulation composition on the in vitro characteristics of hot stage extrudates

Abstract

The aim of this study was to evaluate the influence of the formulation composition on the characteristics of starch based hot stage extrudates in order to obtain high quality and high efficacy matrices for controlled drug delivery. Their characteristics were compared to those of a reference formulation, for which in vivo data were available. The influence of the starch type, the plasticizer and the lubricant were investigated. The extrudates were produced with a twin screw co-rotating extruder equipped with a twin screw powder feeder and a 3 mm cylindrical die. The extrudates were manually cut and dried for 48 h at 60°C prior to analysis. They were characterized by Karl Fischer titration, Hg-porosimetry, 4-point bending and dissolution testing. Changing the formulation composition did not affect the water content or the porosity of the extrudates but had an influence on their mechanical strength and dissolution profiles. These characteristics were particularly dependent on the plasticizer and lubricant concentration used and on the nature of the starch component and the lubricant. Expansion, depending on starch conversion and amylose–lipid complex formation, played a major role in the explanation of the results obtained. All the formulations tested showed a slow drug release profile in vitro. However, the differences with the reference formulation — which was tested in vivo in earlier work — were probably too small to give a distinct improvement of its in vivo behaviour.