Effect of Polymorphic Transformation During the Extrusion-Granulation Process on the Pharmaceutical Properties of Carbamazepine Granules.

Abstract

The effects of a solvent system on the pharmaceutical properties of carbamazepine (CBZ) granules containing a polymorphic form of bulk powder were investigated by X-ray diffraction analysis, thermal analysis, mercury porosimetry and Brunauer-Emmett-Teller (BET) surface area measurement. A powder mixture consisting of 20% CBZ form I, as a bulk powder, 56% crystalline α-lactose monohydrate and 24% corn starch was used as a pharmaceutical powder, with the three kinds of binder solutions (distilled water, 50% aqueous ethanol and ethanol) containing 5% hydroxypropylcellulose (HPC). After kneading with a binder solution, the granules were obtained using an extruding granulator. The X-ray diffraction and differential scanning calorimetry (DSC) results of the granules indicated that form I with 50% ethanol solution transformed into a dihydrate form during extruding granulation, but this did not occur with the distilled water or ethanol solutions. The order of hardness and specific surface area (Sw) of the granules was distilled water>50% ethanol>ethanol and 50% ethanol>ethanol>distilled water. The stress-thickness profiles of the tabletting compression processes of CBZ granules obtained using various binder solution systems were measured, and the initial compression process due to particle rearrangement was affected by the characteristics in the granules. The total pore volume of tablets obtained from 50% ethanol was the lowest, and their order was ethanol>distilled water>50% ethanol. Their order of tablet hardness reflected the total pore volume of the tablet, and was 50% ethanol>distilled water>ethanol. All pharmaceutical properties of the granules and/or tablets containing CBZ were affected by the characteristics of the solvent systems in binder solution.