The mean dissolution time depends on the dose/solubility ratio

Abstract

Purpose: To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model.

Methods: Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a dimensionless quantity by taking into account the volume of the dissolution medium. Our results were applied to in vitro and in vivo data taken from literature.

Results: We found that MDT depends on q when q < 1 and is infinite when q > 1 and that the classic expression of MDT = 1/k. where k is the dissolution rate constant, holds only in the special case of q = 1. For the case of perfect sink conditions, MDT was found to be proportional to dose. Using dissolution data from literature with q < 1, we found better estimates of MDT when dependency on dose/ solubility ratio was considered than with the classic approach. Prediction of dissolution limited absorption was achieved for some of the in vivo drug examples examined.

Conclusion: The mean dissolution time of a drug depends on dose/ solubility ratio, even when the model considered is the simplest possible. This fact plays an important role in drug absorption when absorption is dissolution limited.