Release Kinetics Study of Poorly Water-Soluble Drugs
from Nanoparticles: Are We Doing It Right?
- Publication date
- Publisher
Abstract
<i>In vitro</i> drug release kinetics studies are routinely
performed to examine the ability of new drug formulations to modulate
drug release. The underlying assumption is that the studies are performed
in a sufficiently dilute solution, where the drug release is not limited
by the solubility and the difference in release kinetics profile reflects
the performance of a drug carrier <i>in vivo</i>. This condition
is, however, difficult to meet with poorly water-soluble drug formulations,
as it requires a very large volume of release medium relative to the
formulation mass, which makes it challenging to measure the drug concentration
accurately. These difficulties are aggravated with nanoparticle (NP)
formulations, which are hard to separate from the release medium and
thus require a dialysis bag or repeated high-speed centrifugation
for sampling. Perhaps for these reasons, drug release kinetics studies
of NPs of poorly water-soluble drugs are often performed in suboptimal
conditions in which the NPs are not sufficiently diluted. However,
such a practice can potentially underestimate drug release from NPs,
leading to an inaccurate prediction that the NPs will attenuate the
drug activity <i>in vivo</i>. Here we perform release kinetics
studies of two different NP formulations of paclitaxel, a representative
poorly water-soluble drug, according to common practices in the literature.
We find that the drug release from NPs can be substantially underestimated
depending on the choice of the release medium, NP/medium ratio, and
handling of release samples. We discuss potential consequences of
underestimating drug release, ending with suggestions for future studies
with NP formulations of poorly water-soluble drugs