Injection-molded gastroresistant capsules: preliminary in vivo evaluation

Purpose: a preliminary in vivo evaluation of a gastroresistant (GR) capsular device based on hydroxypropyl methylcellulose acetate succinate (HPMCAS) prepared by injection molding. Methods: 600 µm thick capsules were prepared by means of an injection molding press (BabyPlast 6/10P, Chronoplast, I) from co-milled blends of HPMCAS/polyethylene glycol 1500 and Explotab® CLV (55:22:23 ratio). Two in vivo studies were carried out involving 9 healthy volunteers (26-61 years, 53-87 kg). 1st: an assembled GR system was administered, consisting of an enteric-coated commercially-available capsule (HPMC, size 000; V-Caps®, Capsugel, B) filled with both fenazon powder and an acetaminophen-containing HPMCAS molded unit (IMGR). 2nd: an IMGR unit and an enteric-coated commercially-available capsule (HPMC, size 2; V-Caps®) filled with fenazon were co-administered. These tracer drugs were selected because they can concomitantly be assayed in saliva by gradient RP HPLC. Results: The time of first detection in saliva of the tracer drugs was used to define the in vivo opening time of the relevant dosage forms. Based on data obtained by assembled GR systems, a mean opening time after stomach emptying (defined by fenazon appearance in saliva) of 117 min (CV 43.9) was calculated for IMGR capsules, that can be considered as the time for their intestinal disintegration/ dissolution. Moreover, by comparing IMGR with conventional enteric-coated capsules, an only 35 min longer latency was obtained. Conclusion: HPMCAS-based capsules prepared by injection molding and filled with a drug powder were demonstrated to release their contents within the intestine. As compared with conventional GR capsules, promising results were achieved in terms of in vivo opening time, thus pointing out the possibility of developing advantageous alternatives to coated dosage forms.