In silico simulation of niacin release from lipid tablets: theoretical predictions and independent experiments.

ABSTRACT

A mechanistically realistic mathematical model is presented allowing for the quantification of niacin release from lipid tablets, based on glyceryl dibehenate. The systems were prepared either by direct compression or via hot-melt extrusion/grinding/compression. The model assumptions are based on a thorough physico-chemical characterization of the tablets before and after exposure to the release medium. Importantly, the model allows for the first time for the quantitative prediction of the effects of the composition, dimensions and type of preparation method of the tablets on the resulting niacin release kinetics. These quantitative theoretical model predictions were confirmed by several sets of independent experimental results. Furthermore, in silico simulations revealed the fundamental importance of limited niacin solubility within the lipid tablets during major parts of the release periods, very steep concentration gradients exist and net vitamin flux is restricted to specific regions within the tablets.