Mechanistic understanding of the link between Sodium Starch Glycolate properties and the performance of tablets made by wet granulation.

The impact of varying Sodium Starch Glycolate (SSG) grade and wet granulation intensity on the mechanism of disintegration and dissolution of mannitol-based Immediate Release (IR) placebo tablets was investigated. MRI and 1H NMR provided mechanistic insight, and revealed a four-fold range in both tablet disintegration and dissolution rates. MRI was used to quantify the rates of change in tablet volumes and the data fitted to a hydration/erosion model. Reduced levels of cross-linking change SSG from a swelling to a gelling matrix. The tablet hydration and dissolution rates are related to the viscosity at the tablet-solution interface, with high viscosities limiting mass transport.

Quantitative ultra-fast MRI of HPMC swelling and dissolution.

For the first time quantitative Rapid Acquisition with Relaxation Enhancement (RARE) based ultra-fast two-dimensional magnetic resonance imaging has been used to follow the dissolution of hydroxypropylmethyl cellulose (HPMC) in water. Quantitative maps of absolute water concentration, spin-spin relaxation times and water self-diffusion coefficient are obtained at a spatial resolution of 469 microm in less than 3 min each. These maps allow the dynamic development of the medium release rate HPMC/water system to be followed. It is demonstrated that the evolution of the gel layer and, in particular, the gradient in water concentration across it, is significantly different when comparing the quantitative RARE sequence with a standard (nonquantitative) implementation of RARE. The total gel thickness in the axial direction grows faster than that in the radial direction and that the dry core initially expands anisotropically. Additionally, while HPMC absorbs a large amount of water during the dissolution process, the concentration gradient of water within the gel layer is relatively small. For the first time MRI evidence is presented for a transition swollen glassy layer which resides between the outer edge of the dry tablet core and the inner edge of the gel layer.

A semiquantitative analysis of the effects of cisplatin on the rat stria vascularis.

Cisplatin (CDDP) is a very effective chemotherapeutic agent but is highly ototoxic. Most studies have focused on the effects of CDDP on the outer hair cells. The purpose of this study was to examine changes in the stria vascularis in cisplatin treated male Wistar rats and to provide semiquantitative analysis of the results. We removed a section of the stria vascularis from the basal turn of five control and five CDDP (16 mg/kg) treated rats. Using transmission electron microscopy (TEM) we analyzed: (1) changes to the strial tissue as a whole; and (2) intracellular changes in the marginal cells. We also subjected the samples to semiquantitative analysis using the MCID, focusing on three aspects of strial profile abnormalities; the number of abnormal marginal cells in CDDP treated tissue, intracellular strial edema and densitometry. Controls appeared normal, but many pathologic changes were apparent in the experimental group. Results from the semiquantitative analysis indicate cisplatin has a deleterious effect on the stria vascularis including strial edema; bulging, rupture and/or compression of the marginal cells and depletion of the cytoplasmic organelles.