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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Missel
Paul J
PJ
Drug Delivery, Alcon Research Ltd, Fort Worth, Texas 76134, USA. paul.missel@alconlabs.com
Stevens
Larry E
LE
Mauger
John W
JW
D018481:Convection; D004058:Diffusion; D004780:Environment, Controlled; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011237:Predictive Value of Tests; D012995:Solubility
D004364:Pharmaceutical Preparations