Release performance of injection-molded HPC-based capsules filled with different formulations of a model drug

Purpose. To compare the dissolution and lag time in drug release from hydroxypropyl cellulose (HPC)-based capsules to conventional gelatin and hydroxypropyl methylcellulose (HPMC) capsules. Methods. Capsules made from a mixture of 90:10 HPC (Klucel® LF, Ashland):PEG1500 were produced by injection molding (BabyPlast 6/10P, Cronoplast S.L.). Weight and dimensions for the HPC-based capsules and commercially available size 0 gelatin and HPMC capsules (Capsugel) were determined. Scanning electron microscopy (SEM) was used to image the different capsules. Acetaminophen (AAP) was used as the model drug. Capsules were filled with different formulations of AAP, including fine powder, granules, pellets, and semi-solid. The capsules were then subjected to dissolution testing. Drug release in deionized water at 37°C as a function of time was determined by UV/Vis spectrophotometry. Lag time in drug release (expressed as time for 10% of drug to be released) as well as the time for between 10 and 90% drug release (as a measure of burst effect) were determined. Results. HPC-based capsules were similar in diameter with respect to gelatin and HPMC capsules, but about 7mm shorter in length. The weight of the HPC capsule was noticeably higher than conventional capsules (229 vs ~90 mg), due to the properties of the polymer and the thickness of the capsule shell. With respect to release performance, when AAP fine powder was used as the filling formulation, HPC-based capsules showed a lag time roughly 34 minutes longer than conventional capsules. Moreover, the burst effect observed when evaluating the relevant release patterns was comparable (approximately 5 min). Results were confirmed when capsules were filled with other formulations of AAP. In particular, lag time in drug release from HPC capsules ranged from 36 (±3.36) minutes for fine powder up to 45 (±7.27) minutes for pellets, compared to 3.4 (±1.56) and 6.4 (±7.17) minutes, respectively, for gelatin capsules. Conclusion. The overall results demonstrated that HPC-based capsules exhibit a lag phase of approximately 34 minutes prior to drug release, significantly longer than conventional capsules. These novel capsules confirmed to be useful in delayed drug release applications. Moreover, the lag time in drug release was independent from the filling formulation.