Dissolution test acceptance sampling plans^∗

^∗The views expressed in this paper are the authors' professional opinions. They do not represent the official of the U.S. Food and Drug Administration.

Abstract

The U.S. Pharmacopeia (USP) general monograph provides a standard for dissolution compliance with the requirements as stated in the individual USP monograph for a tablet or capsule dosage form. The acceptance rules recommended by USP have important roles in the quality control process. The USP rules and their modifications are often used as an industrial lot release sampling plan, where a lot is accepted when the tablets or capsules sampled are accepted as proof of compliance with the requirement. In this paper, the operating characteristics of the USP acceptance rules are reviewed and compared to a selected modification. The operating characteristics curves show that the USP acceptance rules are sensitive to the true mean dissolution and do not reject a lot or batch that has a large percentage of tablets that dissolve with less than the dissolution specification.

This is especially true when the mean dissolution is close to the specification. Although the modified USP rule, as proposed by Givand, improves the performance substantially, it is still sensitive to the mean dissolution. In order to have the robustness (to the mean dissolution), we propose an acceptance rule that is based on a sampling-by-measurements approach. It is preferable to the others in both lot discrimination and robustness when the assumption of normality holds.

Keywords:

• Dissolution test
• Sampling inspection
• Operating characteristics
• Threestage test
• Robustness

^∗The views expressed in this paper are the authors' professional opinions. They do not represent the official of the U.S. Food and Drug Administration.

^∗The views expressed in this paper are the authors' professional opinions. They do not represent the official of the U.S. Food and Drug Administration.

Notes

^∗The views expressed in this paper are the authors' professional opinions. They do not represent the official of the U.S. Food and Drug Administration.