A pulsatile drug delivery system based on rupturable coated hard gelatin capsules.

The objective of this study was to develop and evaluate a pulsatile drug delivery system based on drug-containing hard gelatin capsules, which were coated with a swelling layer and an outer insoluble, water-permeable polymeric coating. An inner pressure developed by the swelling layer resulted in the rupture of the outer coating. Preliminary studies with a simulated rupture test demonstrated the dependence of the lag time prior to rupture on the properties of the coating, such as its water permeability and mechanical strength. The lag time increased with a higher coating level, but decreased with the addition of the hydrophilic pore former, hydroxypropyl methylcellulose. Increasing the amount of the swelling layer decreased the lag time. The coated capsules took up release medium at a nearly constant rate until a critical maximum was reached, where the swelling pressure was sufficient to rupture the outer coating. The rate of medium uptake decreased with increasing coating level, while the extent of medium uptake was almost the same for the different coating levels. A hydrophobic particulate material, magnesium stearate, was added to the coating layer to reduce the mechanical strength and therefore the lag time. The test conditions, such as surfactant addition to the release medium or floating vs. complete immersion of capsules in the medium, affected the lag time.