Influence of the Changed USP Specifications on Disintegration Test Performance

The aim of this study was to investigate if the changes made in the specifications of the disintegration procedure impact the performance of the disintegration test described in USP chapters <701> and <2040>. Different tablets and capsules were produced, and their disintegration times were determined. The following disintegration time parameters were analyzed: volume of the immersion fluid, type of apparatus (Apparatus A for method <701>; Apparatus B for method <2040>), and attachment of a wire cloth to the basket assembly. By adjusting the compaction force and lubricant level, the disintegration time of the tablets was standardized to 15 min. The disintegration time change was statistically significant when varying the volume of the immersion fluid. The type of apparatus and the attachment of a wire cloth resulted in no significant difference in the disintegration time of capsules. The USP requirements for immersion medium volume should be strictly followed to obtain correct and reproducible test results. The disintegration test is a suitable performance test for certain pharmaceutical and dietary dosage forms. *Corresponding author. INTRODUCTION Disintegration was the first performance test for solid oral dosage forms required by the Swiss Pharmacopoeia back in 1935 (1). The rationale for disintegration testing is given by the fact that most oral dosage forms need to fragment into powder particles before drug particles are released and dissolved. Yet, disintegration is no direct measure for drug dissolution and cannot be used as a universal in vivo bioavailability predictor (2). The disintegration test simply determines if the solid oral dosage form under investigation disintegrates in a given time frame. However, for BCS class I drugs, disintegration rather than dissolution was lately discussed as a possible performance test (3). The dissolution of class I and class III drugs is not limited within the physiological pH range (4), and here, disintegration can be seen as the critical step for bioavailability (5). Using a Quality by Design (QbD) approach, a correlation between drug particle size and dissolution rate might be established, and subsequently, dissolution testing might be substituted by disintegration testing (3). Due to the establishment of QbD, disintegration might again become an important performance test. According to the USP, disintegration of a pharmaceutical or dietary dosage form is a performance test that is intended to ensure the batch-to-batch consistency of a product. USP 32 describes three different apparatus that can be used to perform a disintegration test. Chapter <701> describes Apparatus A consisting of a basket assembly with six observation cylinders. Chapter <2040> describes Apparatus B, which uses observation cylinders with a larger diameter. Both apparatus are well-established, and their designs have hardly changed over the past decade. Donauer et al. (5) reviewed the current specification changes for the disintegration apparatus and test conditions. USP 32 general chapter <2040> lists a third method for the disintegration of soft-shell capsules. In the “rupture test,” the opening of soft-shell capsules is the performance test criterion. Scientific data describing the disintegration test is limited (6–9). In recent years, USP changed the procedure of the disintegration test and harmonized the chapter <701> with the European and Japanese Pharmacopoeia (10). The test conditions prior to USP 28 only specified that the bottom wire mesh of the observation cylinder should have a distance of at least 25 mm from the bottom of the beaker on the downward stroke and at least 25 mm from the fluid level on the upward stroke. Now, USP states the same downward stroke specification but specifies that the basket assembly should not be totally submerged and the distance of the wire mesh should be at least 15 mm from the fluid level on the upward stroke (Figure 1). In the previous specifications, a wire mesh was applied to keep the dosage forms from floating out of the observation cylinders on the downward stroke, while the new specification makes the upper wire cloth obsolete. However, it is still part of the USP text (11). To the best of our knowledge, the impact of these changes on the performance of the disintegration test has not been investigated. diss-17-01-02.indd 6 2010-2-24 10:02:09 dx.doi.org/10.14227/DT170110P6