Evaluation of the rupture test for stability studies of soft-shell capsules

Abstract

The United States Pharmacopoeia (USP) implemented a rupture test in General Chapter <2040> for the evaluation of soft-shell capsules. It was first published in USP 30–NF 25 in 2007. Nutraceutical manufacturers showed in the past that the rupture test does not work for some of their soft-shell capsule products if a long-term stability test was performed. The present study aimed to evaluate the rupture test as a quality control tool for long-term stability samples using different enzymes, which were introduced in USP 39 for tier-two dissolution testing, and apply it to the rupture test. Commercial hydrophobic, oil-based, oral multivitamin soft-shell capsules were tested using the rupture test according to USP General Chapter <2040>. The same product was tested after 18 months exposure to long-term stability conditions. The stability samples were also tested using immersion media containing pepsin, pancreatin, papain, and bromelain. The commercial product passed the rupture test. The long-term stability samples failed the rupture test in all media including the enzyme-containing medium described for Tier 2 testing. The current study shows that the rupture test is sensitive and can detect gelatin cross-linking in long-term stability samples. From dissolution studies, it is known that in vitro quality control tests might over-discriminate and have limited impact on the in vivo status. Industry needs to develop alternative methods and generate scientific data to demonstrate product performance when long-term stability samples fail the rupture test.