In Vitro and In Vivo Evaluation of an Injection-Molded Capsular Device for Oral Pulsatile Release

A swellable/erodible capsular device for pulsatile/colon delivery based on hydroxypropylcellulose (HPC) was prepared by injection-molding. For this purpose, a bench-top press coupled with a purposely devised mold was employed. Tested for in vitro behavior, capsules with differing shell thicknesses (300, 600 and 900 μm) filled with acetaminophen were proven able to give rise to typical pulsatile release profiles, with lag times (time to 10% release) increasing as a function of thickness. The in vivo performance was evaluated on healthy fasting volunteers. After single dose administration, acetaminophen was assayed in saliva samples collected at predetermined time points. In all cases, the appearance of drug in saliva was delayed with respect to intake, and a fast increase in its concentration was observed thus indicating that the release rate would not be controlled by the swollen capsules. Lag time, calculated as the time to 10% of AUC, was shown to depend on the thickness of the shells. Furthermore, it turned out to correlate linearly with in vitro lag time for all the systems administered. Based on these results, the capsular delivery platform proposed was demonstrated to be potentially suitable for a pulsatile and/or time-dependent colonic release of bioactive compounds.