2 research outputs found
Dissolution of Crystalline Pharmaceuticals: Experimental Investigation and Thermodynamic Modeling
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
Design of Median Crystal Diameter Using Gassing Crystallization and Different Process Concepts
The reproducibility of product properties
of normal batch cooling
crystallizations is often insufficient. For a reliable design of product
properties like the median diameter, it is essential to control the
nucleation process. An innovative technology to induce nucleation
during cooling crystallization is gassing. Therefore, quantification
of the influence of gassing and process parameters is important. For
this purpose, Design of Experiment approaches were used, investigating
a linear cooling profile with constant cooling duration and quadratic
cooling profiles with varied cooling duration. Succinic acid/water
was used as the model system. The supersaturation where gassing is
started was identified as most important design parameter using linear
cooling profiles. Using quadratic cooling profiles, the median diameter
can be mainly designed by adjusting the cooling duration. By the choice
of the cooling profile and gassing supersaturation, it is possible
to control the median diameter in a range between 300 and 750 μm.
The results show also that independent from the cooling profile, gassing
crystallization has an enlarging effect on the median diameter of
product crystals. This effect can be used to reduce batch time for
crystallization processes