Evaluation of lactose based 3D powder bed printed pharmaceutical drug product tablets

Heuvel, Korinde A. van den; Wit, Myrthe T.W. de; Dickhoff, Bastiaan H.J.

doi:10.1016/j.powtec.2021.05.050

Cited by 17 publications

(6 citation statements)

References 15 publications

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“…There is a good correlation between several physical properties of the tablets (crushing strength, dissolution time and weight) and the LS values used in the printing process. As lower LS values correspond to higher liquid amounts, this might result in more consolidation of powder particles, in turn resulting in a solid structure with better physical properties ( Figure 2 ), similar to the results observed in another study [ 29 ]. There is a difference between tablets printed at an LS of 0.50 mm and those printed at 0.40 or 0.45 mm (although not significant with 0.45 mm LS tablets).…”

Section: Discussionsupporting

confidence: 86%

See 1 more Smart Citation

Formulation of a 3D Printed Biopharmaceutical: The Development of an Alkaline Phosphatase Containing Tablet with Ileo-Colonic Release Profile to Treat Ulcerative Colitis

et al. 2022

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Powder bed printing is a 3D-printing process that creates freeform geometries from powders, with increasing traction for personalized medicine potential. Little is known about its applications for biopharmaceuticals. In this study, the production of tablets containing alkaline phosphatase using powder bed printing for the potential treatment of ulcerative colitis (UC) was investigated, as was the coating of these tablets to obtain ileo-colonic targeting. The printing process was studied, revealing line spacing as a critical factor affecting tablet physical properties when using hydroxypropyl cellulose as the binder. Increasing line spacing yielded tablets with higher porosity. The enzymatic activity of alkaline phosphatase (formulated in inulin glass) remained over 95% after 2 weeks of storage at 45 °C. The subsequent application of a colonic targeting coating required a PEG 1500 sub-coating. In vitro release experiments, using a gastrointestinal simulated system, indicated that the desired ileo-colonic release was achieved. Less than 8% of the methylene blue, a release marker, was released in the terminal ileum phase, followed by a fast release in the colon phase. No significant impact from the coating process on the enzymatic activity was found. These tablets are the first to achieve both biopharmaceutical incorporation in powder bed printed tablets and ileo-colonic targeting, thus might be suitable for on-demand patient-centric treatment of UC.

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Section: Discussionsupporting

confidence: 86%

“…Formulations were printed with an in-house-built powder bed printer as described previously [ 29 ]. The 3D structures for the printing tablets were designed with OpenSCAD (version 2019.05) software and then exported to STL format files.…”

Section: Methodsmentioning

confidence: 99%

Formulation of a 3D Printed Biopharmaceutical: The Development of an Alkaline Phosphatase Containing Tablet with Ileo-Colonic Release Profile to Treat Ulcerative Colitis

et al. 2022

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“…Tablets were printed using an in-house-built powder bed printer developed by TNO [ 23 ]. The modeled 3D structures and the printing procedure were the same as previously described by Nguyen et al, as presented in Figure 1 [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

Surface Engineering Methods for Powder Bed Printed Tablets to Optimize External Smoothness and Facilitate the Application of Different Coatings

Nguyen,

Zillen,

van Heijningen

et al. 2023

Pharmaceutics

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In a previous attempt to achieve ileo-colonic targeting of bovine intestinal alkaline phosphatase (BIAP), we applied a pH-dependent coating, the ColoPulse coating, directly on powder bed printed (PBP) tablets. However, the high surface roughness necessitated an additional sub-coating layer [Nguyen, K. T. T., Pharmaceutics 2022]. In this study, we aimed to find a production method for PBP tablets containing BIAP that allows the direct application of coating systems. Alterations of the printing parameters, binder content, and printing layer height, when combined, were demonstrated to create visually less rough PBP tablets. The addition of ethanol vapor treatment further improved the surface’s smoothness significantly. These changes enabled the direct application of the ColoPulse, or enteric coating, without a sub-coating. In vitro release testing showed the desired ileo-colonic release or upper-intestinal release for ColoPulse or enteric-coated tablets, respectively. Tablets containing BIAP, encapsulated within an inulin glass, maintained a high enzymatic activity (over 95%) even after 2 months of storage at 2–8 °C. Importantly, the coating process did not affect the activity of BIAP. In this study, we demonstrate, for the first time, the successful production of PBP tablets with surfaces that are directly coatable with the ColoPulse coating while preserving the stability of the encapsulated biopharmaceutical, BIAP.

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“…When evaluating the processability of powder mixtures in terms of binder jetting technology, flowability, wettability, and consolidation of particles seem to be most important [15,16]. These can be easily measured with established pharmaceutical methodology.…”

Section: Introductionmentioning

confidence: 99%

“…To ensure good particle linkage, the liquid should penetrate into the layer and activate the solid binder. Vertical liquid penetration is critical [16]. Droplets should not remain on the surface, as this can lead to unnecessary surface defects, bad layer interlinkage, and poor spreadability of the powder in the next layer.…”

Section: Introductionmentioning

confidence: 99%

Influence of the Binder Jetting Process Parameters and Binder Liquid Composition on the Relevant Attributes of 3D-Printed Tablets

Kreft

Lavrič

Stanić³

et al. 2022

Pharmaceutics

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Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties of tablets. A model formulation containing the ketoprofen drug was developed and used as a base for optimization. Firstly, important printing parameters were identified with a fractional factorial design. Saturation and layer height critically influenced selected tablet properties. Relevant process parameters were optimized for tablet mechanical strength by using the D-optimization DoE approach. The best mechanical properties were achieved when saturation was set to 1 and layer height to 150 µm. On the other hand, binder ink composition did not appear to impact tablet mechanical strength as much as process parameters did. Three ethanol-water mixtures were tested at three tablet strength levels and no definitive conclusions could be drawn. The binder jetting process can be wasteful, especially if the unbound powder cannot be reused. To determine the suitability of powder blend recycling, the ketoprofen content was measured for 27 subsequent batches of tablets. While the trendline did indicate a slight reduction in ketoprofen content, the powder blend reuse can nevertheless be employed.

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Evaluation of lactose based 3D powder bed printed pharmaceutical drug product tablets

Cited by 17 publications

References 15 publications

Formulation of a 3D Printed Biopharmaceutical: The Development of an Alkaline Phosphatase Containing Tablet with Ileo-Colonic Release Profile to Treat Ulcerative Colitis

Formulation of a 3D Printed Biopharmaceutical: The Development of an Alkaline Phosphatase Containing Tablet with Ileo-Colonic Release Profile to Treat Ulcerative Colitis

Surface Engineering Methods for Powder Bed Printed Tablets to Optimize External Smoothness and Facilitate the Application of Different Coatings

Influence of the Binder Jetting Process Parameters and Binder Liquid Composition on the Relevant Attributes of 3D-Printed Tablets

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