| Interaction of moisture in the solid state of excipients and drugs is an important factor in the formulation, stability, and processing of pharmaceutical dosage forms. Moisture interaction with pharmaceutical excipients and a few drugs has been widely published, but only a few studies deal with moisture interactions with cephalosporins. In the present work, three hydrated oral cephalosporins, Cephradine, Cephalexin, and Cefixime (new third generation oral Cephalosporin) are characterized. Solid state characterization of the three drugs is done by particle morphology, SEM, DSC, TGA, XRD and FTIR. Decomposition pressures at various temperatures are measured and heat of vaporization is calculated. From the vapor pressure data, critical relative humidities are calculated for each hydrate. An isothermal TGA method is developed, and dehydration curves are obtained at different temperatures. Solid state models are used to study dehydration kinetics. Using the rate constants of dehydration, Arrhenius type of plots are generated and activation energy for dehydration of each drug is obtained. Solid state stability of Cefixime was studied at different temperatures and humidity and mechanism for decomposition was proposed. Moisture sorption of the cephalosporins was studied by static and dynamic method. An Inverse Gas Chromatography (IGC) method was developed to study moisture interaction under dynamic conditions. With this method, a variety of moisture sorption isotherms (sorption and desorption curves) can be obtained at different temperatures in a few hours time. Since no long term equilibrium is necessary, this method is very useful in studying repetitive sorption and desorption behavior of pharmaceuticals. Good correlation between literature reported GAB model constants for microcrystalline cellulose, and constants obtained using IGC was obtained. For the cephalosporins, moisture interaction was studied using the dynamic method and hydration and dehydration behaviors were characterized. Sorption data and sorption hysteresis indicated more moisture interaction with Cephradine than Cephalexin and Cefixime. This was consistent with the static method. |
