Is silicified wet-granulated microcrystalline cellulose better than original wet-granulated microcrystalline cellulose?

The purpose of this study was to investigate the effect of granulating water level on the physical-mechanical properties of microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC). Granulations containing either MCC or SMCC were manufactured at different water levels using a high-shear mixer and were then tray-dried. The water level ranged from 0 to 100%. The granules were evaluated for size, granular and true density, porosity, flow, compactibility, compressibility, and strain-rate sensitivity index (SRS). Increasing the water level affected the size, increased the granular density and flow properties of the granules, and decreased the porosity and compactibility. The compactibilities for both materials were similar and acceptable at each granulating water level up to 40%. They both showed poor compactibility at higher water levels. Yield values and SRSs revealed that MCC and SMCC have similar compressibility, and that both exhibit a plastic component to the deformation process. The granulating water level had no statistically significant effect on the compressibility or the SRS for MCC or SMCC. SMCC did not offer practical advantages over MCC, other than better flow in the powder form, which could be attributed to slightly larger particle size and the presence of silicon dioxide in its structure.

Mechanism and kinetics of metal ion-mediated degradation of fosinopril sodium.

Fosinopril sodium (I), a new angiotensin converting enzyme inhibitor, is a diester prodrug of the active moiety II. We report here a novel transformation of fosinopril into beta-ketoamide, III, and a phosphonic acid, IV, mediated through metal ion participation. The interaction of fosinopril with magnesium ions was studied in a solution model system in which methanol was used as the solvent and magnesium acetate as the source of metal ions. Kinetic analysis indicated the degradation to be a bimolecular process, with the rate being first order in both metal ion and fosinopril concentration. The degradation products II, III, and IV effectively retarded the magnesium ion mediated reaction of fosinopril. Based on the results of 31P-NMR, 1H-NMR, Mn(II)-EPR spectroscopy experiments and mass spectrometry, a mechanism is postulated for this transformation. A key reactive intermediate has been characterized that supports the proposed mechanism. The results can account for the observed degradation profile of the fosinopril sodium in a prototype tablet formulation.