Characterization of solid dispersions of carbamazepine and PEG6000/vinylcaprolactam/vinylacetate copolymer

Purpose. to investigate the solid-state properties and dissolution performances of solid dispersions of carbamazepine and a new marketed copolymer proposed for hot melt extrusion. Methods. Physical mixtures [PM] were prepared by mixing in mortar and pestle for 10 min carbamazepine [CBZ, polymorphic form III] and PEG6000/vinylcaprolactam/vinylacetate copolymer (Soluplus® BASF) in various drug/polymer ratios (1:9, 3:7, 1:1, 7:3 w/w). Co-melted formulations [CM] were prepared by heating the PM at 170°C on a hot plate for 15 min, allowing to cool at room temperature and grinding the resulting glasses in a mortar. PXRD study, DSC analysis and dissolution test (paddle apparatus, 500mL of 0.0125% SLS solution, 37±0.5°C, 100 rpm, UV detection at 287 nm) were performed on all samples. Results. drug-polymer solid-state interaction, resulting in complete loss of CBZ crystallinity was found to occur in CM with drug/polymer ratios 1:9 and 3:7 w/w. Accordingly, the glass transition recorded for these dispersions was lowered with respect to that of the pure polymer. Non-interacted crystalline CBZ was detected in all PM as well as in 1:1 and 7:3 CM formulations. Furthermore, non-interacted amorphous CBZ was thought to be present in the 7:3 CM formulation, resulting in drug crystallization up on heating in the DSC experiment. As far as dissolution properties are concerned, PM presented similar or only slightly higher dissolution rate with respect to the pure drug, whilst 1:9 and 3:7 CMF demonstrated a remarkable improvement of dissolution rate (the amount dissolved at t=10min doubled that of the pure CBZ). The 7:3 CM formulation was affected by a decreased dissolution rate probably caused by the formation of CBZ hydrate during the test. Conclusion. solid dispersion of CBZ with a new PEG6000/vinylcaprolactam/vinylacetate copolymer can be successfully prepared by comelting method, resulting in a high degree of drug-polymer interaction and consequently a remarkable improvement of drug dissolution rate.