Improvement of the bioavailability of poorly water-soluble active ingredients is one of the
main challenges in modern pharmacy. This can be achieved with different approaches, one
being by converting the active ingredient from its crystalline to amorphous form, thus
forming an amorphous solid dispersion. This is a single-phase system composed of
molecules of poorly water-soluble active ingredients dispersed or dissolved in one or more
polymeric carriers. The formation of amorphous solid dispersions is particularly important
in terms of solubility and improved bioavailability, as they enable temporarily increased
concentration of the active ingredient during dissolution. One of the most effective
technologies for the preparation of solid dispersions is hot-melt extrusion.
The aim of this master's thesis was to prepare a completely amorphous solid dispersion with
a high percentage of nifedipine (49.5%) and Soluplus® or Kollidon® VA64 as the polymeric
carrier, by varying the process parameters. In the Umetrics MODDE® program we prepared
four experimental designs and presented the results through statistical models. We
investigated how the variation of process parameters affects residual crystallinity, content,
and release rate of the active ingredient in the prepared amorphous solid dispersion.
The results showed that with constant barrel temperature and screw speed, no significant
effect of material feed rate on the percentage of residual crystal was observed. At higher
process temperatures (in the miscibility regime) remaining extrusion parameters had no
effect on the ability to form an amorphous solid dispersion. At lower process temperatures
(in the solubility regime) we approached the melting point of the active ingredient by
applying mechanical energy, which depended on both the barrel temperature (via torque)
and screw speed as well as the material feed rate. We proved that by varying the process
parameters, we can successfully obtain a single-phase and well-miscible system, in which
amorphous nifedipine is effectively dispersed in the polymeric carrier, with no detectable
residual crystal. Statistical models showed that higher barrel temperatures and screw speeds
reduced the percentage of residual crystal. On the other hand, varying process parameters
did not affect the active ingredient content which remained stable across all combinations of
process parameters. The chosen release method was not suitable for studying the release rate
and percentage of released active ingredient. Consequently the results could not be linked to
the residual crystallinity. It was found that the active substance was more soluble in
Kollidon® VA64, as the residual crystal content was lower compared to samples made with
Soluplus® as the polymeric carrier under the same extrusion parameters.
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