Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications

Abstract

There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an "absorption window" or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.

Keywords: absorption window; controlled release; gastric retention; gastroretentive drug delivery systems; patient compliance; stomach.

Figure 1

The human stomach. The figure was created using BioRender (www.biorender.com) (Accessed 2 August 2021).

Figure 2

Intragastric location of the floating drug delivery systems. The figure was created using BioRender (https://www.biorender.com/) (Accessed 3 August 2021).

Figure 3

The polypropylene cylinder system developed by Krögel and Bodmeier [84]. The system consisted of entrapped air surrounded on both sides by drug-containing tablets. The air-filled space ensured a low density of the system, thus enabling its floatation. The figure was created using BioRender (www.biorender.com) (Accessed 2 August 2021).

Figure 4

Scanning electron microscopy (SEM) images demonstrating the porous structure of the gastroretentive sponges before (a) and after (b) compression. The compression did not seem to damage the porous structural framework of the sponges which most likely accounted for their zero floating lag time. Reprinted from International Journal of Pharmaceutics Vol 472, Tadros and Fahmy, Controlled-release triple anti-inflammatory therapy based on novel gastroretentive sponges: Characterization and magnetic resonance imaging in healthy volunteers, Pages 27–39, Copyright 2014, with permission from Elsevier.

Figure 5

Schematic localisation of high-density systems in the stomach. The figure was created using BioRender (www.biorender.com) (Accessed 3 August 2021).

Figure 6

Localisation of mucoadhesive/bioadhesive drug delivery systems in the stomach. The figure was created using BioRender (www.biorender.com) (Accessed 3 August 2021).

Figure 7

Transition of the gabapentin-loaded polymer layer from the folded (a) to the expanded (b) state during in vitro release testing [161]. The present figure combines Figures 11 and 12 from the original research paper [161].

Figure 8

Design of the “Long-acting Pill” technology in its expanded form. The dosage form consists of a water-insoluble elastomeric core and six drug-loaded polymeric arms. Reprinted from Nature Communications Vol 9, Kirtane et al., Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy, Pages 1–13, Copyright 2017, published under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/, accessed on 2 August 2021) (the “License”). No changes were made to the original figure presented as Figure 1a in the original research paper.

Figure 9

Intragastric behaviour of (a) expandable and (b) superporous hydrogel systems. The figure was created using BioRender (www.biorender.com) (Accessed 3 August 2021).

Figure 10

Application of magnetic drug delivery systems for gastric retention purposes. The figure was prepared using BioRender (www.biorender.com) (Accessed 3 August 2021).

Figure 11

Images from 3D X-ray microcomputed tomography showing the non-porous tablet structure before sublimation (A) and the highly porous structure of the gastroretentive layer of the tablets after sublimation (B). Reprinted from International Journal of Pharmaceutics Vol 572, Hwang et al., Swellable and porous bilayer tablet for gastroretentive drug delivery: Preparation and in vitro-in vivo evaluation, 118783 (Pages 1–13), Copyright 2019, with permission from Elsevier.

Figure 12

The film folding patterns in case I (A) bilayer capsules where the furosemide immediate-release film was rolled around the zig-zag-folded controlled-release film and case II (B) bilayer capsule formulations where both films were folded in a zig-zag manner. Reprinted from Acta Pharmaceutica Sinica B Vol 2, Darandale et al., Design of a gastroretentive mucoadhesive dosage form of furosemide for controlled release, Pages 509–517, Copyright 2012, published under a Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by-nc-nd/3.0/, accessed on 2 August 2021). No changes were made to the original figure presented as Figure 1 in the original research paper.