Gyógyszerészet, farmakogenomika, gyógyszerkutatás és tervezés, gyógyszeres kezelés
Vegyészmérnöki tudományok
Solubility and permeability are key parameters for establishing in vitro-in vivo correlation
for poorly water-soluble active pharmaceutical ingredients (APIs). Recent studies
demonstrate that not only solubility, but also effective permeability of the API may
change due to the addition of solubilizing agents, and there is a certain mathematical
relation between these physicochemical parameters. The aim of this study was to show
the importance of early screening of solubility and permeability in presence of additives
in order to achieve the expected bioavailability of the API. In this work, the effect
of surfactants and microenvironmental pH modifiers were in focus, and pimobendan was
chosen as model drug.In the case of pH modifiers, the equilibrium solubility of the
API increased, while the permeability decreased significantly. No negative effect
was observed for two surfactants at low additive levels, but these two additives also
exhibited a slightly negative effect on permeability when used at higher concentrations.
In the simultaneous dissolution-permeation studies the surfactants-containing formulation
was found to have slightly higher flux than the pH-modifier-containing one. It can
be due to the phenomenon that the dissolution of the active substance can be enhanced
by these surfactants without any significant permeability reducing effect.The results
obtained from the present study clearly demonstrate the importance of studying drug-additive
interactions in every step of formulation development and based on these, the selection
of the appropriate quality and quantity of additives. In addition, the results also
underline the significance of performing simultaneous dissolution-permeation studies
to predict bioavailability.
