Abstract
Background
For multidose drug products where quality degradation is a concern, evidence of in-use stability should be specified when applying for marketing authorization. However, currently, there are no specific guidelines for reference concerning in-use stability testing. The purpose of this review was to identify trends in the study of in-use stability of nonsterile dosage forms and to present specific considerations necessary for conducting in-use stability tests.
Area covered
In this paper, in-use stability studies of nonaqueous and water-containing, nonsterile pharmaceutical dosage forms are reviewed. A total of 19 articles met the exclusion and inclusion criteria; 9 articles for nonaqueous formulations and 13 articles for water-containing formulations were identified depending on whether the formulation contained moisture. In the case of active substances, articles involving 21 active substances were identified.
Expert opinion
As a result of the study, we summarized in-use stability study designs and in-use shelf life settings for nonsterile formulations such as formulation (strength), container closure system, storage conditions, testing intervals, withdrawal methods, test measurements, and test results. Based on the review, specific considerations including those for drug characterization, storage conditions and test period, testing intervals, and in-use simulation design (withdrawal method) and test methods are presented in relation to the study of in-use stability of nonsterile dosage forms for reference by the pharmaceutical industry.
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All authors (M.S. Choi, M.K. Jin, H.U. Kim, M.W. Jung, H.L. Yoo, J.H Won and C.W. Cho) declare that they have no conflict of interest.
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Choi, M., Jin, M., Kim, H. et al. Considerations for the design of in-use stability studies of nonsterile pharmaceutical dosage forms: a literature review. J. Pharm. Investig. 52, 501–517 (2022). https://doi.org/10.1007/s40005-022-00578-8
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DOI: https://doi.org/10.1007/s40005-022-00578-8