Instability of drug release from anhydrous theophylline-imcrocrystalline cellulose formulations

Abstract

In the production of anhydrous theophylline-microcrystalline cellulose pellets, extrusion is preceded by wet granulation. Wet granulation also used in the tablet production causes a remarkable decrease in drug release rate accompanied by a conversion of anhydrous theophylline into theophylline monohydrate. Oven drying at 40° C does not seem sufficient to restore this conversion. The formation of additional bindings may be responsible for the decrease in drug release rate instead of the crystal transition. The degree of the further decrease in drug release rate during storage depends on the humidity conditions and the packaging. This instability in pharmaceutical availability seems specific for the combination of theophylline and microcrystalline cellulose. A decrease in dissolution rate is also seen for dry compressed anhydrous theophylline-microcrystalline cellulose blends when stored at high humidity levels. Storage at low humidity levels or the use of another diluent seem to overcome this unpredictable change in drug dissolution rate.