| The objective of this study was to synthesize efficient, directly compressible, controlled release matrix systems. Chitosan citrate complexes of varying viscosities were synthesized and characterized using potentiometric titrations, viscosity measurements, Fourier transform infrared and thermal analysis. Viscosity of the complexes ranged from 1080 to 15000 cps for 2% dispersions.; Differential scanning calorimetry (DSC) of individual complexes, chitosan, citric acid and physical mixtures of both confirmed the presence of complexes by the shift in glass transition temperature and/or disappearance of peaks due to the individual components.; Fourier transform infrared (FTIR) spectroscopy of individual complexes, chitosan, citric acid and physical mixtures of both, confirmed the presence of complexes, by the appearance of peaks due to the functional groups.; DSC studies also helped to predict potential incompatibilities between chitosan citrate complexes and several drug candidates used in controlled release formulations. All of the drugs tested were found to be compatible except for naproxen sodium.; Full and fractional factorial designs were employed to develop sustained release tablets for theophylline, propranolol hydrochloride and indomethacin. Polynomial equations and contour plots expressing the release characteristics as a function of formulation variables were used to elucidate the effects of formulation variables on drug release from these matrix systems. Optimal formulations with release profiles ranging from 12 to 24 hours were designed using the polynomial equations. The predicted dissolution profiles for the optimal formulations were found to be in excellent agreement with the experimental values throughout the entire dissolution time period.; The release mechanism of drugs from these matrix systems appears to be a combination of diffusion and erosion processes as shown by the kinetic treatment of the dissolution data. |
