Influence of different solid-dispersion techniques upon the release of dimenhydrinate from chewing-gum formulations

Solid dispersions and physical mixtures of dimenhydrinate (I) in polyethylene glycol 6000 (PEG 6000) and urea were prepared by co-evaporation (or solvent) and fusion-solvent method to increase its aqueous solubility. In contrast to the very slow dissolution rate of pure (I), the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Drug-polymer interactions in the solid state were investigated by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy. By these physical determinations no drug-polymer interactions were evidenced. Finally the solid-dispersions were used in the chewing gum formulations to improve the poor solubility of pure (I) in saliva during mastication. The aqueous dissolution of (I) in chewing gums was favored by the presence of urea. The addition of TweenF' 80 as the solubilizing agent to the chewing gum, increased the release of (I) about 20%, whereas it only increased the solubility of pure (I) by 3%. Drug release profiles from the chewing gum formulations were compared with TravvellQ Gum as the reference standard. The formulation based on solid-dispersion of (I) with urea and Tween 80 released about 60% of the drug after 60 min with a Higuchi kinetic model.