Application of the melt granulation technique in development of self-emulsifying tablets with immediate release of carbamazepine


The aim was to develop immediate-release carbamazepine tablets consisting of self-emulsified drug delivery system (SEDDS) by using the melt granulation technique, application of Quality by design. The first set of screening experiments investigated the influence of six parameters (meltable binder type; amounts of meltable binder, carbamazepine and crospovidone; carrier type, and compression force) on carbamazepine release rate from tablets, using fractional factorial experimental design. In the second set of experiments, amounts of meltable binder and Cremophor® RH40 were varied according to the central composite design. The optimal formulation which showed the fastest release rate (more than 80% in first 30 min) was identified (compression force of 8 kN, 20% of Labrafil® 2130CS, 10% of Cremophor® RH40, 30% of carbamazepine, 5% of crospovidone NP and Neusilin® UFL2 used as the carrier). Different analytical techniques (DSC, PXRD, FT-IR, Raman spectroscopy) confirmed the maintenance of carbamazepine in its therapeutically active polymorph form III in the optimal formulation. Raman spectroscopy was used to demonstrate the stability of the optimal formulation during the two months stability study (25°С, RH 40%). It can be concluded that melt granulation technique can be used in development of solid-SEDDS with immediate-release of the drug.