Process and formulation variables affecting the performance of a rupturable capsule-based drug delivery system with pulsatile drug release

The objective of this study was to optimize several process and formulation parameters, which influence the performance of a rupturable, pulsatile drug delivery system. The system consisted of a drug-containing hard gelatin capsule, a swelling layer of croscarmellose (Ac-Di-Sol®) and a binder, and an outer ethylcellulose coating. Polyvinyl pyrrolidone (Kollidon 90F) was superior to HPMC and HPC as a binder for the swelling layer with regard to binding (adherence to capsule) and disintegration properties of the swelling layer. The capsule-to-capsule uniformity in the amount of swelling layer and outer ethylcellulose coating, which significantly affected the lag time prior to rupture of the capsule, was optimized by decreasing the batch size, and by increasing the rotational pan speed and the distance between the spray nozzle and the product bed. The type of baffles used in the coating pan also affected the layering uniformity. Fully-filled hard gelatin capsules had a shorter lag time with a higher reproducibility compared to only half-filled capsules, because the swelling pressure was directed primarily to the outer ethylcellulose coating and not to the inner capsule core. Stability studies revealed that the lag time of the capsules was stable over a 240-day period when the moisture content was kept unchanged.