Abstract
Purpose
This study aimed to establish a developmental strategy for swellable and erodible matrix tablets containing mirabegron using a quality by design approach with geometric properties such as gel strength, erosion rate, and swelling rate.
Methods
The design of the experiment (DoE) was used to investigate the effects of critical material attributes (CMAs) on critical quality attributes (CQAs) and geometric properties. Pearson correlation coefficients were used to determine the relationship between geometric properties and CQAs. To evaluate the pharmacokinetics of mirabegron following oral administrations of the test and reference formulations, in vivo pharmacokinetic study was carried out using Beagle dogs.
Results
As a result of DoE, (%) dissolved drug amount and geometric properties were significantly related to CMAs. A robust design space was established with low absolute and relative biases between prediction and experimental results. Pearson correlation coefficients showed significant correlations between (%) dissolved drug amount and geometric properties. The geometric mean ratios of the maximum plasma concentration and area under the concentration–time curve between test and reference formulations were 0.954 and 1.050, respectively. No significant differences in all pharmacokinetic parameters were observed between reference and test drug-treated groups (p < 0.05, t-test).
Conclusion
These results show the usefulness of the developmental strategies using various geometric properties while developing a swellable/erodible matrix tablet.
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All authors (J.Y. Kim, T.H. Kim, E Kim, and D.H. Choi) declare no conflicts of interest.
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The animal experimental protocols were approved, and all animals received care in compliance with the guidelines of the Animal Care Committee of HLB BioStep Co., Ltd. (BIOSTEP IACUC 23-KE-0155).
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Kim, J.Y., Kim, T.H., Kim, E. et al. Developmental strategy for swellable/erodible matrix tablet of mirabegron: quality by design approach with various geometric properties and pharmacokinetic evaluation. J. Pharm. Investig. 53, 881–894 (2023). https://doi.org/10.1007/s40005-023-00642-x
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DOI: https://doi.org/10.1007/s40005-023-00642-x