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Development of Delayed-Release Pellets of Ibuprofen Using Kollicoat® MAE 100P via Hot-Melt Extrusion Technology

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Abstract

Purpose

The present work was intended to develop the ibuprofen-Kollicoat® MAE 100P delayed-release pellets using hot-melt extrusion technology, which exhibits pH-dependent solubility. Ibuprofen irritates the gastric lining, so its release in the gastric environment is not desired. Conventionally, Kollicoat® MAE 100P has been used as an enteric coating polymer, and we have explored its application using hot-melt extrusion technology in our work.

Methods

Three different drug loadings were processed at various extrusion temperatures using HME to produce pellets of uniform size. DSC was performed to study the drug’s state, the polymer’s thermal behavior, and drug-polymer miscibility. An in vitro drug release study was performed in 0.1N HCl followed by pH 6.8 phosphate buffer to understand the ability of the polymer to impede the release of ibuprofen in the stomach. Furthermore, the lead batch was characterized by DSC, FTIR, HS-PLM, and optical microscopy to study the interaction between the drug and polymer.

Results

The thermogram of the pellets indicated no drug-polymer immiscibility. This work also demonstrates proof of the plasticizing ability of ibuprofen. Drug release studies showed less than 1.5% drug release in 0.1N HCl in 2 h, and complete drug release was obtained in the next 2 h in pH 6.8 phosphate buffer, indicating the delayed-release characteristics of the pellets.

Conclusion

This work proves that Kollicoat® MAE 100P could be used in modified-release dosage forms to attain the delayed-release pellets.

Graphical Abstract

Schematic representation of development of ibuprofen delayed release pellets

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Acknowledgements

We are deeply grateful to the late Dr. Suresh Bandari for his contributions to this research. He provided instrumental guidance to the project at crucial steps and helped to move it forward.

Funding

This project was partially supported by the National Institute of General Medical Sciences (NIGMS; Grant Number P30GM122733), which is a component of the National Institutes of Health (NIH) serving as one of its Centers of Biomedical Research Excellence (COBRE).

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Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS, 38677, USA

    Mittal Darji, Adwait Pradhan, Sateesh Kumar Vemula & Michael A. Repka

  2. BASF SE, R&D Product Management Excipients, Ludwigshafen, 67056, Germany

    K. Kolter

  3. BASF Corporation, 500 White Plains Road, Tarrytown, NY, USA

    Nigel Langley

  4. Pii Center for Pharmaceutical Technology, The University of Mississippi, Oxford, MS, 38677, USA

    Michael A. Repka

Authors
  1. Mittal Darji
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  2. Adwait Pradhan
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  4. K. Kolter
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  5. Nigel Langley
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  6. Michael A. Repka
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Contributions

Mittal Darji: design experiment, acquire data, analyze data, and interpret data, manuscript writing. Adwait Pradhan: acquire data, analyze data, and interpret data. K. Kolter and Nigel Langley: funding acquisition, resources. Sateesh Kumar Vemula and Michael A. Repka: interpret data, and draft manuscript. Michael A. Repka: supervise the study.

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Correspondence to Michael A. Repka.

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Darji, M., Pradhan, A., Vemula, S.K. et al. Development of Delayed-Release Pellets of Ibuprofen Using Kollicoat® MAE 100P via Hot-Melt Extrusion Technology. J Pharm Innov 18, 1827–1837 (2023). https://doi.org/10.1007/s12247-023-09758-x

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