In vivo performance of molded capsules for enteric release

Purpose A preliminary study of the in vivo performance of a molded capsular device intended for enteric release of the contents. Methods Co-milled blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) / polyethylene glycol 1500 and Explotab® CLV (55:22:23 ratio) were prepared to be processed in a micro-molding press (BabyPlast 6/10P, Chronoplast, I) equipped with a capsular mold (closed capsule height, 13 mm; diameter, 8 mm; wall thickness, 600 µm). Two different in vivo studies were performed on 9 healthy volunteers. The 1st study involved the administration of an assembled system consisting of an enteric-coated commercially-available capsule (HPMC, size 000; V-Caps®, Capsugel, B) filled with fenazon powder and a molded unit containing acetaminophen. In the 2nd study an analogous molded unit and an enteric-coated commercially-available capsule (HPMC, size 2; V-Caps®, Capsugel, B), filled with fenazon, were co-administered. Tracer drugs were selected because they can concomitantly be assayed in saliva by gradient RP HPLC. The in vivo opening time of the dosage forms was defined by the time of first detection in saliva of the relevant tracer. Results Data obtained from the administration of the assembled system allowed the assessment of a mean opening time of molded capsules after stomach emptying, defined by fenazon appearance in saliva, of 117 min (CV 43.9). This time frame can be assumed as the time needed for their intestinal disintegration/dissolution. Subsequently, a comparison between a conventional enteric-coated system and the HPMCAS-based molded unit was carried out in the same study, and a 35 min mean difference of the relevant opening times was observed. Conclusion HPMCAS-based capsular devices prepared by micro-molding and filled with a drug powder were demonstrated suitable for enteric release. In terms of in vivo opening time, satisfactory results were achieved as compared with capsules provided with a conventional enteric coating. These findings are in agreement with literature data, which generally indicate up to 2 hours for the complete disintegration/dissolution of gastroresistant dosage forms in the intestine, and suggest the use of the molded device as a possible alternative to coated systems.