Evaluation of bioadhesive gels for local action in the esophagus

Direct drug administration to the esophagus faces several obstacles, including continuous salivary dilution and removal of the dosage form from the tissue surface due to esophageal peristalsis. These actions often result in short exposure times and reduced concentrations of drug at the esophageal surface, providing limited opportunities for drug absorption into or across the esophageal mucosa. A variety of bioadhesive polymers were investigated for their ability to resist removal by salivary washings using an ex vivo porcine esophageal tissue model. Hydroxypropylmethylcellulose and carboxymethylcellulose both have reported bioadhesive properties, but neither was able to withstand repeated exposure to saliva, and the gels formulated with these polymers were quickly removed from the esophageal surface. Two polyacrylic polymers, carbomer and polycarbophil, also showed limited esophageal surface retention when exposed to salivary washing, likely due to the ionic composition of saliva affecting the inter-polymer interactions necessary for these polymers to maintain their increased viscosities. In situ gel forming polysaccharide gels (ion-triggered), including xanthan gum, gellan gum, and sodium alginate, showed superior tissue surface retention, and formulations containing these bioadhesive polymers along with ciclesonide, an anti-inflammatory soft prodrug, were investigated as potential, locally-acting esophageal delivery systems. Exposure of a segment of esophagus to the ciclesonide-containing gels resulted in therapeutic concentrations of des-ciclesonide, the active drug metabolite, in the tissues within 30 min. Increasing des-CIC concentrations were also observed over a 3-hour exposure interval suggesting continued release and absorption of ciclesonide into the esophageal tissues. These results demonstrate the ability to achieve therapeutic drug concentrations in the esophageal tissues using in situ gel-forming bioadhesive polymer delivery systems, and these systems provide promising opportunities for the local treatment of esophageal disease.