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. 2020 Jan 17;12(1):77.
doi: 10.3390/pharmaceutics12010077.

Fabrication of Intragastric Floating, Controlled Release 3D Printed Theophylline Tablets Using Hot-Melt Extrusion and Fused Deposition Modeling

Bhupendra Raj Giri  1 , Eon Soo Song  1 , Jaewook Kwon  1 , Ju-Hyun Lee  2 , Jun-Bom Park  2 , Dong Wuk Kim  1
Affiliations

Fabrication of Intragastric Floating, Controlled Release 3D Printed Theophylline Tablets Using Hot-Melt Extrusion and Fused Deposition Modeling

Bhupendra Raj Giri et al. Pharmaceutics. .

Abstract

This work presents a novel approach for producing gastro-retentive floating tablets (GRFT) by coupling hot-melt extrusion (HME) and fused deposition three-dimensional printing (3DP). Filaments containing theophylline (THEO) within a hydroxypropyl cellulose (HPC) matrix were prepared using HME. 3DP tablets with different infill percentages and shell thickness were developed and evaluated to determine their drug content, floating behavior, dissolution, and physicochemical properties. The dissolution studies revealed a relationship between the infill percentage/shell thickness and the drug release behavior of the 3DP tablets. All the developed GRFTs possessed the ability to float for 10 h and exhibited zero-order release kinetics. The drug release could be described by the Peppas-Sahlin model, as a combination of Fickian diffusion and swelling mechanism. Drug crystallinity was found unaltered throughout the process. 3DP coupled with HME, could be an effective blueprint to produce controlled-release GRFTs, providing the advantage of simplicity and versatility compared to the conventional methods.

Keywords: controlled release; dissolution kinetics; fused deposition modeling 3D printing; gastro-retentive floating system; hot-melt extrusion; theophylline.

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Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
SEM images of hot-melt extruded filament. (A) Exterior appearance (30×) and (B) cross sectional shape (40×).
Figure 2
Figure 2
3D tablet design templates, tablet photographs, and SEM images of 3D printed tablet surface with (A) constant shell thickness (0.8 mm), different infill percentages (T1 30%, T2 20%, T3 10%, and T4 0%) and (B) constant infill percentage (20%), different shell thickness (T5 1.2 mm, T2 0.8 mm, T6 0.4 mm, and T7 0 mm).
Figure 3
Figure 3
DSC curves of free THEO, hydroxypropyl cellulose (HPC), physical mixture (PM), THEO-HPC filament, and 3DP tablet. PM represents the physical mixture of THEO, HPC, and stearic acid (SA) at a 30:70:7 (w/w/w) ratio.
Figure 4
Figure 4
PXRD curves of 3DP tablet, THEO-HPC filament, PM, SA, HPC, and free THEO.
Figure 5
Figure 5
Photographs of 3DP tablet (T2) floating in dissolution medium (0.1 N HCl solution) at room temperature.
Figure 6
Figure 6
Drug release profiles of the 3DP tablets; (A) showing the influence of the infill percentages and (B) showing the influence of the shell thickness. Each value represents the mean ± standard deviation (n = 3).
Figure 7
Figure 7
Swelling contribution (R) to the diffusion contribution (F), R/F ratio from T3, T4, T5, and T6.
Figure 8
Figure 8
Linear fitting of drug release from T3, T4, T5, and T6 over 10 h.
See this image and copyright information in PMC

References

    1. Streubel A., Siepmann J., Bodmeier R. Drug delivery to the upper small intestine window using gastroretentive technologies. Curr. Opin. Pharmacol. 2006;6:501–508. doi: 10.1016/j.coph.2006.04.007. - DOI - PubMed
    1. Shah H.P., Prajapati S.T. Quality by design based development and optimization of novel gastroretentive floating osmotic capsules of clopidogrel bisulfate. J. Pharm. Investig. 2019;49:295–311. doi: 10.1007/s40005-018-0405-5. - DOI
    1. Lamichhane S., Park J.B., Sohn D.H., Lee S. Customized Novel Design of 3D Printed Pregabalin Tablets for Intra-Gastric Floating and Controlled Release Using Fused Deposition Modeling. Pharmaceutics. 2019;11:564. doi: 10.3390/pharmaceutics11110564. - DOI - PMC - PubMed
    1. Chavanpatil M.D., Jain P., Chaudhari S., Shear R., Vavia P.R. Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for ofloxacin. Int. J. Pharm. 2006;316:86–92. doi: 10.1016/j.ijpharm.2006.02.038. - DOI - PubMed
    1. Klausner E.A., Lavy E., Friedman M., Hoffman A. Expandable gastroretentive dosage forms. J. Control. Release. 2003;90:143–162. doi: 10.1016/S0168-3659(03)00203-7. - DOI - PubMed

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