Bioavailability and Bioequivalence of Locally Acting Colon-Targeted Products: In Vivo and In Vitro Considerations

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (15 October 2021) | Viewed by 12539

Special Issue Editors


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Guest Editor
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29/39 Brunswick Square, London WC1N 1AX, UK
Interests: biopharmaceutics; physiology of the gastrointestinal tract; formulation and modified release; oral drug delivery; colonic targeting; drug metabolism; drug absorption; gamma scintigraphy

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Guest Editor
1. Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, D-55099 Mainz, Germany
2. Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA
Interests: dissolution; disintegration; buffer; oral drug delivery; modified release; biopharmaceutics

Special Issue Information

Dear Colleagues,

Targeting drug release to the colon has been a major research topic over the past three decades. Potential applications for colon-targeted products include localized therapy of colonic pathologies (e.g., inflammatory bowel disease and colon cancer). Multiple approaches to colonic delivery exist, such as pH-dependent, microbe-dependent, time-dependent and pressure-dependent drug delivery systems. One of the aspects that sets localized drug delivery apart from systemic drug delivery is the fact that the site of action is located before systemic circulation, making the value of traditional bioavailability and bioequivalence studies questionable. This is sometimes compounded by the poor colonic permeability of many drug substances, resulting in drug release and availability at the site of action being poorly reflected by the drug plasma concentration profile (if observable), which is then shaped by the strong rate-limiting permeation step. Therefore, research into alternative in vivo approaches as well as into in vitro testing methods that exhibit satisfactory in vivo predictivity (preferably without entailing high complexity) is often needed.

Prof. Dr. Abdul Basit
Dr. Jozef Al-Gousous
Guest Editors

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Keywords

  • colon targeting
  • local drug delivery
  • bioavailability
  • bioequivalence
  • drug release

Published Papers (3 papers)

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Research

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14 pages, 32351 KiB  
Article
Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers
by Sarah Sulaiman, Pavel Gershkovich, Caroline L. Hoad, Matthew Calladine, Robin C. Spiller, Snow Stolnik and Luca Marciani
Pharmaceutics 2022, 14(2), 270; https://doi.org/10.3390/pharmaceutics14020270 - 24 Jan 2022
Cited by 5 | Viewed by 3096
Abstract
Oral specially coated formulations have the potential to improve treatment outcomes of a range of diseases in distal intestinal tract whilst limiting systemic drug absorption and adverse effects. Their development is challenging, partly because of limited knowledge of the physiological and pathological distal [...] Read more.
Oral specially coated formulations have the potential to improve treatment outcomes of a range of diseases in distal intestinal tract whilst limiting systemic drug absorption and adverse effects. Their development is challenging, partly because of limited knowledge of the physiological and pathological distal gastrointestinal factors, including colonic chyme fluid distribution and motor function. Recently, non-invasive techniques such as magnetic resonance imaging (MRI) have started to provide novel important insights. In this feasibility study, we formulated a coated capsule consisting of a hydroxypropyl methylcellulose (HPMC) shell, coated with a synthetic polymer based on polymethacrylate-based copolymer (Eudragit®) that can withstand the upper gastrointestinal tract conditions. The capsule was filled with olive oil as MRI-visible marker fluid. This allowed us to test the ability of MRI to track such a coated capsule in the gastrointestinal tract and to assess whether it is possible to image its loss of integrity by exploiting the ability of MRI to image fat and water separately and in combination. Ten healthy participants were administered capsules with varying amounts of coating and underwent MRI imaging of the gastrointestinal tract at 45 min intervals. The results indicate that it is feasible to track the capsules present in the gastrointestinal tract at different locations, as they were detected in all 10 participants. By the 360 min endpoint of the study, in nine participants the capsules were imaged in the small bowel, in eight participants in the terminal ileum, and in four in the colon. Loss of capsule integrity was observed in eight participants, occurring predominantly in distal intestinal regions. The data indicate that the described approach could be applied to assess performance of oral formulations in undisturbed distal gastrointestinal regions, without the need for ionizing radiation or contrast agents. Full article
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11 pages, 3079 KiB  
Article
Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery
by Annemarie Broesder, Said Y. Bircan, Anneko B. de Waard, Anko C. Eissens, Henderik W. Frijlink and Wouter L. J. Hinrichs
Pharmaceutics 2021, 13(12), 1985; https://doi.org/10.3390/pharmaceutics13121985 - 23 Nov 2021
Cited by 7 | Viewed by 2539
Abstract
The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse [...] Read more.
The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified. Full article
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29 pages, 12048 KiB  
Review
In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications
by Mauricio A. García, Felipe Varum, Jozef Al-Gousous, Michael Hofmann, Susanne Page and Peter Langguth
Pharmaceutics 2022, 14(2), 291; https://doi.org/10.3390/pharmaceutics14020291 - 26 Jan 2022
Cited by 9 | Viewed by 5955
Abstract
Several locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action located before systemic circulation and troublesome colonic sampling, [...] Read more.
Several locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action located before systemic circulation and troublesome colonic sampling, there is room for the introduction of meaningful in vitro methods for development, quality control (QC) and regulatory applications of these formulations. A one-size-fits-all method seems unrealistic, as the selection of experimental conditions should resemble the physiological features exploited to trigger the release. This article reviews the state of the art for bio-predictive dissolution testing of colon-targeted products. Compendial methods overlook physiological aspects, such as buffer molarity and fluid composition. These are critical for pH-dependent products and time-controlled systems containing ionizable drugs. Moreover, meaningful methods for enzymatic-triggered products including either bacteria or enzymes are completely ignored by pharmacopeias. Bio-predictive testing may accelerate the development of successful products, although this may require complex methodologies. However, for high-throughput routine testing (e.g., QC), simplified methods can be used where balance is struck between simplicity, robustness and transferability on one side and bio-predictivity on the other. Ultimately, bio-predictive methods can occupy a special niche in terms of supplementing plasma concentration data for regulatory approval. Full article
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