Comparison of the Rupture and Disintegration Tests for Soft-Shell Capsules

The USP General Chapter <2040> Disintegration and Dissolution of Dietary Supplements introduced a rupture test as a performance test of soft-shell capsules. Traditionally, the disintegration test was used for determining the disintegration time of all solid oral dosage forms. The aim of this investigation was to investigate differences between the rupture test and the disintegration test using soft-shell capsules. Five different soft-shell capsule products were chosen based on their filling contents and treated to simulate a production deficiency. The study design compared capsules as received with capsules that were treated by coating them with the liquid contents of another capsule. The capsules were incubated at room temperature and at 40 °C. The tests were repeated after two weeks, and at each time point, twelve capsules of each product were tested using the rupture and the disintegration tests. Six capsules were tested untreated, while the other six capsules were treated. Rupture and disintegration times were recorded as dependent variables in each experiment. The data were analyzed using ANOVA. According to the USP definition for disintegration, the rupture of a soft-shell capsule can be seen as fulfilling the disintegration criterion if the capsule contents is a semisolid or liquid. Statistical analysis showed no advantage of the rupture test over the disintegration test. On a product-by-product basis, both tests were sensitive to certain investigated parameters. A noticeable difference between both tests was that in most cases, the rupture test reached the defined endpoint faster than the disintegration test. Soft-shell capsules that are subject to a Quality by Design approach should be tested with both methods to determine which performance test is the most appropriate test for a specific product. INTRODUCTION Quality by Design (QbD) is a scientific approach that uses statistical methods for product design, quality testing (1), and predicting product performance from early product development to final product release (2). QbD is highly dependent on the appropriateness of test methods used and can only be successfully applied if a test is sensitive to the parameter that is tested. The performance testing of soft-shell capsules is rather a challenge because the contents of soft-shell capsules can vary from solids to liquids (3). Dissolution methods used for solid oral dosage forms might not be appropriate for soft-shell capsules that have liquid or semisolid contents (4). USP General Chapter <701> Disintegration describes the procedure to evaluate disintegration of oral dosage forms (5). The requirements of disintegration are met if all test units disintegrate or if not more than two units out of a total of 18 units fail to disintegrate within a predetermined time period. USP General Chapter <2040> Disintegration and Dissolution of Dietary Supplements uses a rupture test as performance test of soft-shell capsules (6). In 2002 the rupture test was first published in Pharmacopeial Previews (7), then forwarded to USP’s In-Process Revision (8), and in 2007 it was finally published in USP 30–NF 25. USP 32 lists 14 monographs that use the rupture test performed in dissolution Apparatus 2 (paddle) operated at 50 rpm with 500 mL of water as the immersion medium. The test requirements are met if all capsules rupture within 15 min or if not more than 2 of the total of 18 capsules tested rupture in more than 15 but not more than 30 min. For any other oral dietary supplement dosage form, disintegration test Apparatus A or B is used if the monograph requires disintegration. Another difference is that for hard-shell capsules, Chapter <2040> lists USP pH 4.5 buffer as the immersion medium while Chapter <701> lists water as the default medium if a monograph does not specify any other medium (Figure 1) (9). USP Chapter <2040> also lists Apparatus B, which is intended for dosage forms greater than 18 mm in diameter. Currently there are no scientific data available that compare the performance of the rupture test with that of the disintegration test. The aim of this study was to evaluate if there are advantages in using the rupture test over the disintegration test. A series of experiments was performed and statistical analysis was used to determine differences between the tests. diss-18-01-13.indd 21 2/25/2011 5:48:44 PM dx.doi.org/10.14227/DT180111P21