Enteric-coating of pulsatile-release capsules prepared by injection molding

Purpose. To evaluate hydroxypropylcellulose (HPC)-based capsular devices prepared by injection molding (IM) as substrates for the application of a gastroresistant coating, in comparison with conventional capsules. Methods. Capsules were prepared by IM (BabyPlast 6/10P, Cronoplast S.L.) from a 90:10 HPC (Klucel® LF, Ashland):polyethylene glycol 1500 blend. HPC-based, commercially available size 0 gelatin and HPMC capsules (Capsugel) were filled with 80 mg of acetaminophen. Samples of the three types of capsules were manually sealed with aqueous polymer solutions of the same shell material. Coating suspension (weight %): Eudragit® L 30 D55 (64.10), TEC (3.85) and deionized water (32.05). A Hi-coater (Vector Corporation LDCS) equipped with a perforated coating pan was used. Samples with theoretical weight gains of 4, 6, 8, 10 mg of dry polymer/cm2 were withdrawn during the coating process. Scanning electron microscopy (SEM) images were taken of the coated and uncoated capsules. The release performance was evaluated according to USP 34 (Dissolution Test for Delayed-Release Dosage Forms) and the amount of drug released was determined by UV/Vis spectrophotometry at 248 nm. Results. IM capsules showed a surface rougher than that of gelatin and similar to that of HPMC ones; hence, acceptable adhesion properties of the coating film onto the cores could be expected like for traditional HPMC cores. Indeed, a good correspondence between the actual and the theoretical amount of applied polymer was achieved by adjusting process conditions. A sealing step was not required to achieve enteric resistance. The lag time of coated HPC-based systems increased with respect to that of uncoated cores (̴ 40 min) and was further increased with higher amounts of polymer applied. For the systems coated up to the maximum level, the ability to withstand the acidic medium was confirmed. Moreover, their lag time (~168 min) seems compatible with the maintenance of a release behavior after the pH change analogous to that of the uncoated IM cores. Conclusion. The possibility of obtaining a gastroresistant pulsatile-delivery device based on IM capsules was demonstrated. This approach is promising for the development of time-dependent colonic delivery systems.