The influence of polymeric excipients on desupersaturation profiles of active pharmaceutical ingredients 1: Polyethylene glycol

Polymeric excipients have proven to be beneficial in stabilizing supersaturated solutions of poorly soluble active pharmaceutical ingredients (APIs). They are therefore considered an important tool in improving oral bioavailability of such APIs. To better understand this effect, desupersaturation of two model APIs – naproxen and indomethacin– were investigated with up to 1 wt% of polyethylene glycol (PEG) in aqueous solution.

A crystal-growth model is proposed that allows simultaneous differentiation between thermodynamic and kinetic effects. It could be revealed that PEG, independent of molecular weight and concentration, acts as a solubilizer, thus increasing the equilibrium solubility of the API and thereby reducing the thermodynamic driving force for crystal growth from supersaturated solutions.

In contrast, PEG does not change the kinetic crystal-growth parameters. This theoretical approach allowed predicting the API crystal-growth-dominated desupersaturation profiles in the presence of PEG at different concentrations only using the kinetic crystal-growth parameters determined for polymer-free systems and API solubilities measured in the presence of PEG. Continue on The influence of polymeric excipients on desupersaturation profiles of active pharmaceutical ingredients