The optimization of a manual dissolution method and its equivalence to automated dissolution

In vitro dissolution assays are used to study how a pharmaceutical formulation will behave in vivo. The assay is performed to estimate how the API of the dosage form is released in the body after administration. A previous ATT transfer of Crestor showed a significant difference in the dissolution results between the manual and automatic method, leading to the manual method of Crestor failing to transfer. Only the automatic dissolution analysis was established at AstraZeneca Sweden Operations. The aim of the study was to optimise the manual dissolution method of the immediate-release tablet with USP apparatus II (paddle). The optimisation of the manual dissolution method was initiated with a replication of original issues of the method, where the previously observed problem during the ATT transfer was not recreated. An equivalence study of the manual method was therefore initiated. The equivalence study showed that the manual dissolution method for Crestor of the strengths 5, 10 and 20 mg could claim equivalence to the automatic dissolution method. However, the strength of 40 mg could not claim equivalence, which may be due to the fact that a too small sample size was used and that the data obtained for the strength was insufficient. The strength of 40 mg needs to be further analysed to obtain data with the same sample size as for the other strengths to determine with certainty whether Crestor 40 mg can claim equivalence or not