For details of this model, one should consult the original paper. (Oh, et al., 1993) A summary will be presented here so that the reader has the background to understand the subsequent discussion.
Conceptually, MiMBA involves placing a dispersed suspension of drug particles at the beginning of a cylindrical tube representing the intestinal tract. As the particles traverse the intestine, dissolution of the particles occurs, increasing the concentration of drug within the tube. Simultaneously, absorption takes place, effectively decreasing the drug concentration within the tube. This is shown schematically in Figure 1. The trade off between dissolution and absorption dictates the time course of the drug concentration in the intestine. At the end of the intestinal tube, the total fraction absorbed is calculated by subtracting from the initial dose everything remaining inside the intestine, i.e., the fraction remaining as solid particles and the fraction that dissolved but did not get absorbed.
Mathematically, MiMBA utilizes three dimensionless variables that encompass the physical and chemical properties of the drug as well as the physiological system in which dissolution and absorption takes place. These variables are then incorporated into a system of two differential equations, one describing the fate of the particles' radii, the other describing the concentration along the intestinal tract. The equations can be solved using a mathematical or engineering software package such as MathCad® (Mathsoft, Inc.) or Mathematica® (Wolfram Research, Inc.), and total fraction absorbed calculated.
The three dimensionless variables are described below and deal respectively with the solubilization process, the absorption process, and the dissolution process.
Was this article helpful?