Tensioactivity and Supramolecular Organization of the Palmitoyl Prodrug of Timolol

Purpose. To improve the bioavailability of the ocular drug timolol by facilitating its transport through the cornea, an amphiphilic prodrug was synthesized via the addition of a palmitic chain by esterification. The present study was undertaken to investigate the physicochemical and tensioactive properties of the prodrug.Methods. The amphiphilic properties of the prodrug were firstly investigated by the Wilhelmy plate method. The textures generated by the supramolecular organizations of the ester were visualized by optical microscopy.Results. The prodrug clearly decreased the surface tension. Optical microscopy provided excellent evidence for the existence of lyotropic liquid crystalline phases: two isotropic but organized phases and a birefringent lamellar phase.Conclusions. The results from the ensemble of studies undertaken to determine the amphiphilic properties of the prodrug were all in accord with its ability to form liquid crystalline phases. The liquid crystalline state of the prodrug is believed to introduce a delay in the drug pharmacological effect.