Evaluation of Individual and Crystal Population Dissolution Rates by Time-Resolved X-ray Microtomography.

The intrinsic dissolution rate (IDR) is an important parameter in pharmaceutical science that measures the rate at which a pure crystalline active pharmaceutical ingredient dissolves in the absence of diffusion limitations. Traditional IDR measurement techniques do not capture the complex interplay between particle morphology, fluid flow, and dissolution dynamics. The dissolution rate of individual particles can differ from the population average because of factors such as particle size, surface roughness, or exposure of individual crystal facets to the dissolution medium. The aim of this work was to apply time-resolved X-ray microtomography imaging and simultaneously measure the individual dissolution characteristics of a large population of crystalline particles placed in a packed bed perfused by the dissolution medium. Using NaCl crystals in three different size fractions as a model, time-resolved microtomography made it possible to visualize the dissolution process in a custom-built flow cell. Subsequent 3D image analysis was used to evaluate changes in the shape, size, and surface area of individual particles by tracking them as they are dissolved. Information about the particle population statistics and intrabatch variability provided a deeper insight into the dissolution process that can complement established IDR measurements.

Azobisisobutyronitrile loaded on mesoporous silica particles: A new stressor for solid-state oxidative forced degradation studies.

A new approach for testing drug sensitivity to autooxidative degradation in the solid state is demonstrated in this work. A novel solid-state form of stressing agent for autooxidation has been proposed, based on azobisisobutyronitrile loaded into mesoporous silica carrier particles. The new solid-state form of the stressing agent was applied in degradation studies of two active pharmaceutical ingredients: bisoprolol and abiraterone acetate. The effectiveness and predictivity of the method were evaluated by comparing impurity profiles with those obtained by traditional stability testing of commercial tablets containing the investigated APIs. The results obtained by the new solid-state stressor were also compared with those obtained by an existing method for testing peroxide oxidative degradation in the solid state using a complex of polyvinylpyrrolidone with hydrogen peroxide. It was found that the new silica particle-based stressor was able to effectively predict which impurities could be formed by autooxidation in tablets and that this new approach is complementary to methods for testing peroxide oxidative degradation known from the literature.

Drug loading to mesoporous silica carriers by solvent evaporation: A comparative study of amorphization capacity and release kinetics.

The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of the porous carrier, the loading method, or the attempted mass fraction of the API. At present, there is no established methodology for the rational selection of these parameters. In the present work, we report a systematic comparison of four well-characterised silica carriers and seven APIs loaded by the same solvent evaporation method. In each case, we find the maximum amorphization capacity by x-ray powder diffraction analysis and measure the in vitro drug release kinetics. For a selected case, we also demonstrate the potential for bioavailability enhancement by a permeation essay.