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.

Introduction

Oral drug administration is the most advantageous route for gastrointestinal tract (GIT) treatments. Accounting for ~90% of the global pharmaceutical market, this route is favored by patients and healthcare professionals due to ease of use, non-invasiveness, self-administration, and cost-effectiveness.

This drug delivery route serves two primary purposes: systemic treatments and localized interventions. For systemic treatments, drugs must be absorbed through the highly vascularized gastrointestinal mucosa, entering systemic circulation . This absorption is a complex process involving drug dissolution in gastrointestinal fluids and permeation through the intestinal wall, which can significantly limit drug bioavailability.

In local interventions, oral formulations offer the advantage of reducing systemic side effects by minimizing hepatic metabolism and systemic drug distribution of active pharmaceutical ingredients (API). Therefore, this approach has been crucial for the treating diverse gastrointestinal conditions, including stomach and colorectal cancers, infections, inflammations, bowel diseases, gastro-duodenal ulcers, and gastroesophageal reflux disorders.

However, successful API-targeted delivery requires pharmaceutical formulations capable of navigating the unique and challenging environments of different GIT sections (Fig. 1). Each region presents distinct physiological conditions, including variations in pH, enzymatic activity, bacterial presence, and mechanical forces that can compromise drug integrity and efficacy. For instance, the stomach presents an acidic environment (pH 1–3.5), enzymatic degradation (pepsin), variability in gastric emptying, prolonged retention, and mechanical stress from peristalsis, all of which can destabilize drugs. In the small intestine, enzymatic activity (e.g., trypsin, lipase), pH variability (6–7.5), and rapid transit times limit the absorption window, while gut microbiota in the distal small intestine may alter drug efficacy.

Unlike these organs, the colon is an ideal structure for drug delivery due to its long retention time and the presence of a complex mucosa that facilitates absorption. Nevertheless, formulations targeting the colon must withstand and navigate the diverse physiological and chemical conditions of the upper GIT. Strategies for achieving this delivery often involve the use of inactive prodrugs that are cleaved and activated through hydrolysis in the colon, or the development of colon-specific biodegradable systems using materials like alginate, chitosan, pectin, guar gum, and starch that act as a pH-sensitive coating that protect the API until they reach the colon. For poorly absorbable drugs, mucoadhesive materials have proven effective in prolonging contact with the colonic mucosa.

Advanced approaches include the use of multi-particulate systems composed of small units or materials at the nanoscale capable of passing through the GIT to reach the colon quickly, and specialized coatings that protect APIs from the extreme conditions of the upper GIT while delaying their release until the colon . Nano-drug delivery is a rapidly advancing field, leveraging lipid-based systems, metallic nanoparticles, polymeric materials, and hydrogels for the delivery of phytochemicals and chemotherapeutics.

Nanomaterials in delivery systems offer advantages over traditional methods including improved efficacy, reduced toxicity, and enhanced bio-distribution . Notable commercially available formulations include Rapamune®, a formulation that includes nanoparticles to improve the solubility and bioavailability of sirolimus, a drug used primarily for preventing organ transplant rejection ; Aprepiant® and EMEND®, stable nanostructures used for preventing nausea and vomiting caused by chemotherapy ; TriCor®, used to treat high levels of cholesterol and triglycerides in the blood contains fenofibrate nanoparticles with an average particle size of ~412 nm, which significantly improves the drug’s solubility compared to conventional micronized formulations ; and Triglide®, other solid oral formulation that contains fenofibrate nanoparticles and is used to treat high cholesterol and high triglyceride levels in adults.

Despite these advancements, there remains a lack of commercial nanomaterial-based systems specifically designed to target the colon. Therefore, this work aims to provide a comprehensive scientific and technological analysis of current strategies for the development of oral dosage forms for drug delivery of therapeutics into the colon, using scientific and patent databases along with a bibliometric analysis and bibliographical review of the latest advances related to oral dosage forms to identify new technologies and their technological maturity level.

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3.2.2 Excipients

Pharmaceutical excipients are constituents of a dosage form other than APIs [61]. Although excipients are inactive compounds, they have multiple functions permitting the efficient manufacturing of dosage forms and affecting the physical and chemical characteristics of active drug ingredients and their bioavailability. Principal examples of excipients include carriers, coating agents, binders, plasticizers, modified release agents, disintegrants, lubricants, and surfactants, as shown in Fig. 6. For the review of recent advances in the excipients by functionality, only coatings, carriers, modifying release agents, and surfactants were deepened, as they are the most reported in the research articles. More information about the functions of excipients and which are the most used, both in research articles and patents, is shown in (Table 3).

Table 3 Main attributes and applications of principal excipients used for the development of oral dosage forms

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Martínez, E., Gamboa, J., Finkielstein, C.V. et al. Oral dosage forms for drug delivery to the colon: an existing gap between research and commercial applications. J Mater Sci: Mater Med 36, 24 (2025). https://doi.org/10.1007/s10856-025-06868-5