Development of a pressure-sensitive glyceryl tristearate capsule filled with a drug-containing hydrogel.

The purpose of this work was to develop a new pressure-sensitive dosage form that breaks and releases its content in a fasted stomach at the predominant pressure at the pylorus. The content of the dosage form should be liquid so that the active pharmaceutical ingredient quickly reaches maximum absorption in the upper small intestine. For this purpose glyceryl tristearate capsules were developed, consisting of an extremely brittle shell, with a crushing behavior that can be controlled by modification of the shell thickness. The capsules were filled with a hydroxyethyl cellulose gel containing paracetamol. Dissolution testing using USP apparatus 2, performed for simulating the resting time in the stomach, did not show any release. Studies using a texture analyser showed a correlation between the glyceryl tristearate filling volume and the necessary force to break the capsule. Physiological conditions in dissolution testing, such as movement, pressure and discontinuous medium contact, were set in a stress test device and showed that the dosage forms did not break and release its pharmaceutical ingredient until a pressure of 300 mbar was applied which served as a threshold limit for physiological pressure occurring during gastric emptying of large solids.