Purpose. To develop a new approach for describing drug dissolution which does not require the presuppositions of time continuity and Fick's law of diffusion and which can be applied to both homogeneous and heterogeneous media. Methods. The mass dissolved is considered to be a function of a discrete time index specifying successive `'generations'' (n). The recurrence equation: Phi(n+1) = Phi(n) + r(1 - Phi(n))(1 - Phi(n)X(0)/theta) was derived for the fractions of dose dissolved Phi(n) and Phi(n+1) between generations n and n + 1, where r is a dimensionless proportionality constant, X-0 is the dose and theta is the amount of drug corresponding to the drug's solubility in the dissolution medium. Results. The equation has two steady state solutions, Phi(ss) = 1 when (X-0/theta) less than or equal to 1 and Phi(ss) = theta/X-0 when (X-0/theta) > 1 and the usual behavior encountered in dissolution studies, i.e. a monotonic exponential increase of Phi(n) reaching asymptotically the steady state when either r < theta/X-0 < 1 or r < 1 < theta/X-0. Good fits were obtained when the model equation was applied to danazol data after appropriate transformation of the time scale to `'generations''. The dissolution process is controlled by the two dimensionless parameters theta/X-0 and r, which were found to be analogous to the fundamental parameters dose and dissolution number, respectively. The model was also used for the prediction of fraction of dose absorbed for highly permeable drugs. Conclusions. The model does not rely on diffusion principles and therefore it can be applied under both homogeneous and non-homogeneous conditions. This feature will facilitate the correlation of in vitro dissolution data obtained under homogeneous conditions and in vivo observations adhering to the heterogeneous milieu of the GI tract.

The current analysis of gastrointestinal absorption phenomena relies on the concept of homogeneity. However, drug dissolution, transit and uptake in the gastrointestinal tract are heterogeneous processes since they take place at interfaces of different phases under variable stirring conditions. Recent advances in physics and chemistry demonstrate that the geometry of the environment is of major importance for the treatment of heterogeneous processes. In this context, the heterogeneous character of in vivo drug dissolution, transit and uptake is discussed in terms of fractal concepts, Based on this analysis, drugs are classified in accordance with their gastrointestinal absorption characteristics into two broad categories i.e. homogeneous and heterogeneous. The former category includes drugs with satisfactory solubility and permeability which ensure the validity of the homogeneous hypothesis. Drugs with low solubility and permeability are termed heterogeneous since they traverse the entire gastrointestinal tract and therefore are more likely to exhibit heterogeneous dissolution, transit and uptake. The high variability of whole bowel transit and the unpredictability of conventional dissolution tests for heterogeneous drugs are interpreted on the basis of the fractal nature of these processes under in vivo conditions. The implications associated with the use of strict statistical criteria in bioequivalence studies for heterogeneous drugs are also pointed out.