Rolled-up gastroretentive oral dosages for controlled release of riboflavin and propranolol

Abstract

We present a simple approach to make gelatin gastroretentive oral dosages for controlled release of riboflavin and propranolol. The approach is based on rolling-up of thin self-adhesive gelatin films, on which the reservoirs of the drugs are formed by casting. The radial position of the reservoir and, hence, the lag time and the rate of the drugs release are determined by the lateral position of the reservoir on the film before rolling. Gelatin is stabilized against dissolving in the gastric environment by enzymatic cross-linking mediated by transglutaminase (Tgase). The dosages, which have the form of tight scrolls, are stabilized against unrolling by the crosslinking of the consecutive layers. The scrolls swell in the release media, Fasted State Simulated Gastric Fluid (FaSSGF), to the dimensions which make difficult their passage by the human pyloric sphincter, but remain mechanically robust to resist the stomach peristaltic contractions during at least 24 h, sufficient for the drug release. Eventually the scrolls are degraded by the release media and can be evacuated from the stomach.