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Time-Lapse Macro Imaging with Dissolution Tests for Exploring the Interrelationship Between Disintegration and Dissolution Behaviors of Solid Dosages

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Abstract

Objective

This study aims to establish a Flow-through Visualization Dissolution System (FVDS) that combines time-lapse macro-imaging and a flow-through cell to simultaneously elucidate dissolution and disintegration profiles.

Methods

Three cefaclor extended-release tablets (CEC-1, CEC-2, CEC-3) from different manufacturers were subjected to dissolution tests using both the US Pharmacopeia basket method and the FVDS method. Two dissolution media plans were implemented in FVDS: i) Plan I involved dissolution in pH1.0 medium for 12 h; ii) Plan II initiated dissolution in pH1.0 medium for 1 h, followed by pH6.8 phosphate buffer for 11 h. The resulting dissolution data were fitted using classic mathematical models. Pixel information was further extracted from images obtained using FVDS and plotted over time.

Results

The basket method showed the cumulative dissolution of all three tablets in pH1.0, pH4.0 and water reached 80% within 6 h, but remained below 60% in the pH6.8 medium. The f2 values indicated CEC-2 was similar to CEC-1 in the pH4.0 medium, pH6.8 medium and water. Using FVDS with medium plan II, the cumulative dissolution of CEC-1 and CEC-2 reached about 80% showing similarity, while no similarity was observed between CEC-3 and CEC-1. The f2 factor of the percentage area change profiles also showed consistent results in the dissolution profile of medium plan II. However, FVDS with medium plan I cannot distinguish between CEC-2 and CEC-3.

Conclusion

FVDS offers an alternative to traditional dissolution methods by integrating imaging analysis as a complementary tool to disintegration and dissolution testing methods.

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Data Availability

The authors declare that the data supporting the findings of this study are available in the paper and its Supplementary Information files.

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Acknowledgements

Authors are grateful for the financial support from Sichuan University (“0-to-1” project), 111 project (B18035) and the Fundamental Research Funds for the Central Universities.

Funding

Li Deng received funding support from Sichuan University (“0-to-1” project).

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Author notes

  1. Yichen Yang and Jiajia Gengji contributed equally.

Authors and Affiliations

  1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China

    Yichen Yang, Jiajia Gengji, Tao Gong, Zhirong Zhang & Li Deng

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  1. Yichen Yang
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Contributions

Yichen Yang: Writing—Original Draft, Methodology, Validation, Investigation. Jiajia Gengj: Writing—Original Draft, Formal analysis. Tao Gong: Funding acquisition. Zhirong Zhang: Funding acquisition. Li Deng: Conceptualization, Supervision, Project administration.

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Correspondence to Li Deng.

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Yang, Y., Gengji, J., Gong, T. et al. Time-Lapse Macro Imaging with Dissolution Tests for Exploring the Interrelationship Between Disintegration and Dissolution Behaviors of Solid Dosages. Pharm Res 41, 387–400 (2024). https://doi.org/10.1007/s11095-024-03655-9

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