Crystallization of Amorphous Nifedipine Under Isothermal Conditions: Inter-laboratory Reproducibility and Investigation of the Factors Affecting Reproducibility

High inter-laboratory reproducibility is required for conducting collaborative experiments among several laboratories. The primary aim of our evaluation of the physical stability of amorphous drugs, conducted in co-operation with eight laboratories, was to establish a protocol for isothermal storage tests to obtain data of the same quality from all the participating laboratories. Sharing a protocol that contained the same level of detail as the experimental section of general papers was insufficient for high inter-laboratory reproducibility. We investigated the causes of variations in the data from the various laboratories and restricted the protocol step-by-step to achieve high inter-laboratory reproducibility. The various experimentalists had very different levels of awareness regarding how to control the temperature of a sample as the samples were transferred into and out of thermostatic chambers. Specific instructions on how to conduct this operation, such as regarding the time required for the transfer and thermal protection of the container during the transfer, helped to reduce variation. Improved inter-laboratory reproducibility revealed that the physical stabilities of amorphous drugs differed when samples were prepared in differently shaped aluminum pans designed for various differential scanning calorimeters.(c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

High inter-laboratory reproducibility is crucial for collaborative experiments among multiple laboratories. In this study, we aimed to establish a protocol for isothermal storage tests to ensure consistent data quality from all participating laboratories. Sharing a detailed protocol similar to the experimental section of general papers was not sufficient for achieving high inter-laboratory reproducibility. By investigating the causes of data variations among laboratories, we gradually refined the protocol to improve reproducibility. Specific instructions on sample temperature control during transfer contributed to reducing variability. Our findings also revealed differences in the physical stabilities of amorphous drugs when prepared in differently shaped aluminum pans designed for various differential scanning calorimeters.