Formulation design of carbamazepine fast-release tablets prepared by melt granulation technique

Abstract

This work describes a new approach to prepare a fast-release dosage form for carbamazepine (CBZ), involving the use of melt granulation process in high shear mixer for the production of tablets. In particular, the granules containing CBZ were prepared using polyethylene glycol (PEG) 4000 as a melting binder and lactose monohydrate as a hydrophilic filler. The potential of the intragranular addition of crospovidone as a dissolution enhancer and a disintegrant agent was also evaluated. After the analysis of their solid state performed by means of X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC), the granules were characterised from the technological and dissolution point of view. The subsequent step encompassed the preparation and the evaluation of the tablets, including the effect of the extragranular introduction of crospovidone. Besides the remarkable enhancement of drug dissolution rate of the granulates in comparison to physical mixtures and pure drug, no significant differences were found between the dissolution profiles of the granulates containing lactose or crospovidone. However, the difficult disintegration and bad dissolution performance of the tablets not containing intragranular crospovidone highlight the necessity of this disintegrant in the granulating mixture. Moreover, the extragranular addition of a small amount of crospovidone gave rise to a further amelioration of the disintegration and dissolution performances.