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

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

doi:10.3390/pharmaceutics12010077

Bhupendra Raj Giri, Jun-Bom Park + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics12010077

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Journal: Pharmaceutics	Publication Date: Jan 17, 2020
Citations: 64	License type: CC BY 4.0

Affiliation: Kyungpook National University, Sahmyook University

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.

Highlights

The limitations of orthodox oral drug delivery systems such as fast emptying time and incomplete absorption due to physiological variations, unpredictable gastrointestinal (GI) transit and emptying times as well as metabolic degradation in the lower GI tract, resulting in inferior pharmacokinetics with therapeutic failure for a few drugs [1]
The development of gastro-retentive drug delivery systems (GRDDS) was brought into the limelight in order to overcome the above constraints by retaining drugs in the stomach for an extended period, ensuring optimal bioavailability
Gas needs to be liberated and entrapped first; this system shows floating after a lag time, resulting in the risk of premature emptying of the dosage form from the stomach

Summary

Introduction

The limitations of orthodox oral drug delivery systems such as fast emptying time and incomplete absorption due to physiological variations, unpredictable gastrointestinal (GI) transit and emptying times as well as metabolic degradation in the lower GI tract, resulting in inferior pharmacokinetics with therapeutic failure for a few drugs [1]. This scenario has led to a scientific undertaking to identify better alternatives. The gastro-retentive floating tablet (GRFT) is a low-density system with enough buoyancy to remain afloat above the gastric content in the stomach for a prolonged and pre-determined period of time without interference from the normal peristalsis of the GI tract.

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