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Three-Dimensional Printing of Repaglinide Tablets: Effect of Perforations on Hypromellose-Based Drug Release

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Abstract

Purpose

Drug release from hypromellose-based tablets involves the formation of characteristic dry cores surrounded by outer gel layers in aqueous media. The aim of this study was to investigate the effect of perforation sizes on the dissolution of repaglinide from three-dimensionally (3D) printed tablets with two viscosity grades of hypromellose as rate-controlling polymer.

Methods

Printing pastes of appropriate consistency were developed and fed into a bioplotter cartridge to extrude strands/filaments. Tablets were printed in a crisscross pattern with 1.0, 1.3, and 1.6 mm of inter-strand distances. Printed tablets were characterized and repaglinide dissolution data were evaluated mathematically.

Results

Scanning electron microscopy images confirmed the sealing of the defect-free strands. Differential scanning calorimetry studies indicated potential interaction of ingredients above 150 °C which suggested that the formulation, printing, and drying of tablets should be performed at room temperature. All of the tablets possessed acceptable size, shape, and mechanical strength. Repaglinide dissolution data were evaluated by similarity factor (f2), dissolution efficiency, and two-way analysis of variance (ANOVA) which revealed that drug release rate and extent could be gradually increased by increasing the perforation sizes inside the tablets. Korsmeyer-Peppas modeling of dissolution data showed that the drug release rate approached zero-order kinetics and the release mechanism was Super Case II. This mechanism implies that an outer layer of HPMC gel limits the swelling of the characteristic HPMC tablet cores.

Conclusion

The cores in HPMC tablets usually remain dry for long time in aqueous media. Higher perforation sizes enhanced repaglinide dissolution rate from such tablets. This led us to conclude that different perforation sizes in the tablets must have caused differences in the structural consistency of the core. Perforation sizes played the dominant role over HPMC viscosity grades in determining repaglinide release.

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Acknowledgements

This work belongs to the thesis, “Three-dimensional Printing of Antidiabetic Tablets,” completed in the program of “Masters in Drug and Cosmetics Production Technologies,” Institute of Health Sciences, Yeditepe University, Istanbul, with Ahmed Wadi as the researcher and Dr. Muhammed Abdur Rauf as the adviser. We sincerely thank Prof. Dr. Gamze Torun Köse from the Department of Genetics and Bioengineering, Yeditepe University, for providing access to the EnvisionTEC 3D-Biopltter. We also thank Prof. Dr. Çetin Taş from the Department of Pharmaceutical Technology of the same university.

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Authors and Affiliations

  1. Institute of Health Sciences, Yeditepe University, Istanbul, Turkey

    Ahmed Wadi

  2. Faculty of Pharmacy, Kocaeli Health and Technology University, Yenikoy Mahallesi Ilica Caddesi No:29, Basiskele, 41275, Kocaeli, Turkey

    Muhammed Abdur Rauf

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Contributions

Both authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ahmed Mohammed Wadi. Organization of material supply and workflow, drafting of the work and revising it critically for important intellectual content were performed by Dr Muhammed Abdur Rauf. The first draft of the manuscript was written by Dr Muhammed Abdur Rauf and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Muhammed Abdur Rauf.

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Wadi, A., Rauf, M.A. Three-Dimensional Printing of Repaglinide Tablets: Effect of Perforations on Hypromellose-Based Drug Release. J Pharm Innov (2022). https://doi.org/10.1007/s12247-022-09684-4

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