Oral dosage forms for drug delivery to the colon: an existing gap between research and commercial applications

Abstract

Oral drug administration is the preferred route for pharmaceuticals, accounting for ~90% of the global pharmaceutical market due to its convenience and cost-effectiveness. This study provides a comprehensive scientific and technological analysis of the latest advances in oral dosage forms for colon-targeted drug delivery. Utilizing scientific and patent databases, along with a bibliometric analysis and bibliographical review, we compared the oral dosage forms (technology) with the specific application of the technology (colon delivery) using four search equations. Our findings reveal a gap in the publications and inventions associated with oral dosage forms for colon release compared to oral dosage forms for general applications. While tablets and capsules were found the most used dosage forms, other platforms such as nanoparticles, microparticles, and emulsions have been also explored. Enteric coatings are the most frequently applied excipient to prevent the early drug release in the stomach with pH-triggered systems being the predominant release mechanism. In summary, this review provides a comprehensive analysis of the last advancements and high-impact resources in the development of oral dosage forms for colon-targeted drug delivery, providing insights into the technological maturity of these approaches.

Fig. 1

Obstacles in the GIT for oral dosage forms targeting the colon. Adapted from [77]. Created in https://BioRender.com

Fig. 2

Bibliometric analysis of the number of a research articles (1960–2023), and b patents (1985–2023) reported, according to the technology (oral dosage forms) and its specific application (colon delivery and controlled release). Data represent all countries

Fig. 3

The top 10 countries publishing the most scientific articles and patents related to a, b the technology (oral dosage forms), and c, d the specific application (oral dosage forms for colon-controlled release), respectively

Fig. 4

Word Cloud graphics of a drug dosage forms, b excipients by functionality, c release mechanisms, d APIs, and e characterization techniques in research articles (left) and patents (right). The size of the letters is directly related to the frequency in which the research articles and patents mention the terms (the larger the font, the higher the frequency)

Fig. 5

Parameters reported in patents using Eq. 4, related to oral dosage forms for colon-controlled release. It shows that the parameters that most influence the development and properties of the oral dosage forms are pH, time, and the particle size. Data obtained from PatentInspiration

Fig. 6

Sankey diagram of the relationship between excipients and materials, in a research articles and b patents. The greater the width of the line, the greater the relationship between the terms and the number of times that the excipients were used. The overlapping terms mean that there are shared applications between the categories, resulting in lines converging

Fig. 7

Sankey diagram of the relationship between release mechanism vs oral dosage forms, in a research articles and b patents. The greater the width of the line, the greater the relationship between the terms and the number of times that the release mechanism and the oral dosage form were mentioned by authors and inventors. The overlapping terms mean that there are shared applications between the categories, resulting in lines converging

Fig. 8

Sankey diagram of the relationship between oral dosage form vs manufacturing process, in a research articles and b patents. The greater the width of the line, the greater the relationship between the terms and the number of times that the manufacturing technique and the oral dosage form were mentioned by the authors and inventors. The overlapping terms mean that there are shared applications between the categories, resulting in lines converging

Fig. 9

CPC classifications of the 163 patents found using the search equation

Fig. 10

Strategies for colon-targeted drug delivery tablets: single-layer coatings and double-layer coatings. Single-layer coatings use an enteric material to protect the API from gastric conditions, the thickness depends on the average percentage content used in the formulation phase. Double-layer coatings combine an enteric layer with a time-delay polymer, offering enhanced control over drug release by delaying delivery until the tablet reaches the colon. These approaches emphasize the importance of optimizing coating thickness during formulation to ensure effective and precise drug release. Created in https://BioRender.com

Fig. 11

Release mechanisms of oral dosage forms. Internal (colonic enzymes, microbiota, ROS, pH) or external (light, magnetic fields, temperature) stimuli come into contact with the oral dosage form and produce different responses such as disintegration, degradation, erosion, swelling, diffusion, or osmosis, which allows for dissolution of the API into the colonic environment

Fig. 12

Future perspectives on colon-targeted drug delivery systems. Detailed information is provided in [7, 8, 113] Created in https://BioRender.com