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

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.

Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form.

The aim of this research was to use a ram extruder to prepare directly a fast release dosage form with uniform shape and density, containing carbamazepine (C) as a water-insoluble drug and polyethylene glycol 4000 (PEG) as a low melting binder. The potential inclusion of lactose (L) as a hydrophilic filler was also considered. The temperature suitable to ensure a successful extrusion process of several formulations containing PEG in different percentages was found to be below the melting point of the PEG. The influence of composition on the extrusion process of different ram speeds was checked by measuring the pressure at the steady state, the apparent shear rate and the apparent shear stress of a range of mixtures of drug, lactose and PEG. The physical-mechanical properties of extrudates, including tensile strength and Young's modulus, prepared with different ram velocities were also determined. The solid-state physical structure by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) was established. The dissolution of the extrudates and their corresponding physical mixtures were compared. The mixtures were found to be shear thinning when extruded; the tensile strength of extrudates was dependent on the composition but not the extrusion rate, while the value of Young's modulus was strongly influenced by the rate of extrusion, but less affected by the composition of the extrudates. The results of DSC and XRD indicated that the solid structure of the extrudates corresponded to that of a physical mixture of the components, hence there had been no change in the physical form of the drug induced by extrusion. In terms of dissolution, the rate of the extrusion process did not influence the performance of the products, whereas the composition did. The extruded mixtures of an equivalent composition exhibited a more rapid release than a simple physical mixture. The addition of lactose reduced the dissolution rate.