In situ-forming oleogel implant for rivastigmine delivery.

PURPOSE

To provide a simplified dosing schedule and potentially reduce side effects associated to peak plasma concentrations, an in situ-forming oleogel implant was studied for the sustained-release of rivastigmine.

MATERIALS AND METHODS

The gel was prepared by dissolving 5-10% (w/w) N-stearoyl L: -alanine methyl ester (SAM) organogelator in safflower oil containing either dissolved rivastigmine or its dispersed hydrogen tartrate salt. Rheological analysis, differential scanning calorimetry, and infrared spectroscopy were carried out to assess the impact of drug incorporation on the oleogel; this was followed by in vitro and in vivo release studies.

RESULTS

A weakening of intermolecular interactions was suggested by gel-sol transition temperature drops of 10-15 degrees C upon incorporation of dissolved drug. Meanwhile, the dispersed drug salt induced minimal or no changes in transition temperature. Gels containing dispersed rivastigmine had the lowest burst in vitro (<15% in 24 h). In vivo, the 10% SAM formulation containing dispersed rivastigmine provided prolonged drug release within the therapeutic range for 11 days, with peak plasma levels well below the toxic threshold and up to five times lower than for the control formulation.

CONCLUSIONS

This study established SAM gels to be a promising option for sustained-release formulations in the treatment of Alzheimer's Disease.