Dissolution
of Crystalline Pharmaceuticals: Experimental
Investigation and Thermodynamic
Modeling
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Abstract
In
this work, a two-step chemical-potential-gradient model based
on nonequilibrium thermodynamic principles was developed to investigate
the dissolution mechanism of crystalline active pharmaceutical ingredients
(APIs). The perturbed-chain statistical associating fluid theory was
used to calculate the required solubilities and chemical potentials
of the investigated APIs. The statistical rate theory was used to
describe the mass-transfer rate of the APIs at the solid–liquid
interface during the dissolution process. Dissolution profiles of
indomethacin, naproxen, and glibenclamide in water and in buffered
solutions at pH 5.0, 6.5, and 7.2 were measured using a rotating-disk
system (USP II). The specific dissolution mechanisms of the APIs,
such as surface reaction and diffusion, were analyzed by applying
the proposed model to identify the rate-controlling step. The results
show that the dissolution mechanisms of indomethacin, naproxen, and
glibenclamide change with varying pH values of the solution medium.
On the basis of the calculated rate constants, the dissolution profiles
were modeled with a high degree of accuracy when compared with the
experimental data