Reexamination of convective diffusion/drug dissolution in a laminar flow channel: accurate prediction of dissolution...

The convective diffusion/dissolution theory applied to flowthrough dissolution in a laminar channel was reexamined to evaluate how closely it can predict release rate for a model compound on an absolute basis--a comparison that was lacking from the original literature observations reported from this technique.

The theory was extended to allow for a finite flux of dissolving material, replacing the fixed concentration by a flux condition on the dissolving surface. The derivation introduces a new parameter, k(s), an area-independent analog of the dissolution rate constant defined in the USP intrinsic dissolution procedure.

The release rate for ethyl-p-aminobenzoate originally observed fell within 10% of the absolute prediction assuming a solubility limited situation, and deviated from this prediction in a manner possibly consistent with a finite flux-limited condition, with k(s) approximately 10(-4) M s(-1). For materials exhibiting lower k(s) values, the derivation suggests that at high flow rates, a limit occurs where dissolution rate becomes independent of shear rate and merely a function of solubility and surface area.

The new parameter k(s) may be deduced from any set of geometric and flow conditions, provided the fluid velocity can be determined everywhere in the domain.