Effects of Moisture and Fillers on the Processability and Solid State Properties of Carbamazepine Pellets

Abstract

Carbamazepine pellets containing microcrystalline cellulose (binary pellets) and with the inclusion of -cyclodextrin or lactose fillers (ternary pellets) were obtained by extrusion/spheronization. The effect of the moisture limit on the processability and product performance was investigated by means of the Response Surface Methodology. Lower concentrations of filler and higher water content resulted in an increase in the usable yield (600-1180 m) and mean particle size of the pellets.-cyclodextrin led to lower particle size compared to lactose. Satisfactory flow, compressibility and sphericity were found for all formulations. The dissolution efficiency and T 50% ranged from 68.11 to 83.66% and 1.88 to 10.30 hours, respectively. The higher concentrations of both fillers led to increased dissolution efficiency and decreased T 50% . Higher levels of water led to decreased dissolution efficiency and increased Higuichi r 2 and T 50% values. -cyclodextrin enhanced the dissolution efficiency compared to lactose, and decreased the T 50% value. The higher the -cyclodextrin content the higher the release of the drug in the first hour; however, higher levels of water decreased drug release. The negative effect of the water content on the dissolution behavior could not be completely clarified even following X-ray Powder Diffraction, Differential Scanning Calorimetry and Diffuse Reflectance Infrared Fourier Transform Spectroscopy analysis. It can be speculated that the presence of water leads to a more cohesive structure, hindering the processes of diffusion from the inside of the cores when the maximum limit for water was employed.