The Impact of Plasticizer on the Drug Supersaturation Maintenance by Polymer

Objective

One of the widely used methods to inhibit precipitation and provide supersaturation stabilization of poorly water-soluble drugs in aqueous solution is the use of polymers. To enhance the precipitation inhibitory effect of a polymer, its fast dissolution is a prerequisite, while many polymers have extended-release profiles. The present study investigates the impact of four plasticizers, including glycerol (GLY), polyethylene glycol 400 (PEG), methylparaben (MP) and propylparaben (PP), on the supersaturation stabilization of cinnarizine (CNZ) as a poorly water-soluble drug using eudragit S100 (Eu) as a polymeric precipitation inhibitor.

Methods

The supersaturation behavior of CNZ in the presence of Eu, plasticizers, plasticizer/Eu physical mixtures, and plasticized Eu was evaluated and compared to identify the effect of plasticizers on the Eu-mediated supersaturation stabilization of CNZ.

Results

For MP, PP and PEG, when the plasticizers were physically blended with Eu, no significant improvement in CNZ supersaturation was found compared to Eu alone. However, plasticized Eu with each of these plasticizers resulted in much higher supersaturation stabilization of CNZ compared to polymer alone, which might be due to the higher dissolution rate of polymer with plasticizer. Contrarily, GLY, irrespective of the mode of addition to Eu, led to lower supersaturation stabilization of CNZ by Eu, which might be due to its interaction with Eu which impedes the preventing effect of Eu on the drug precipitation.

Conclusion

From these results, incorporating a suitable plasticizer into a polymer can have a strong advantage in further enhancing the drug supersaturation stabilization by the polymer.