Colon targeting
Due to the increased incidence of inflammatory bowel diseases (IBD), most commonly Crohn’s disease and ulcerative colitis, colon targeted drug delivery systems for oral administration gained importance over the last decades. The oral administration route is preferred due to its non-invasive character and convenience for the patient. Additionally, selective release of biologic drugs to the large bowel has been proposed as a viable strategy to enhance their local bioavailability compared to gastric and/or small intestinal delivery via conventional peroral dosage forms. Eurofins CDMO offers tailor-made solutions for oral colon targeted delivery of small molecules and biologics, intended for local or systemic treatment.
Colon targeting strategies
Classical approaches which are usually based on a pH-triggered or time-controlled polymeric coating of a drug loaded core (tablet, capsule or multiparticulate system) can be applied. pH-triggered coatings are resistant to acidic gastric pH and start to dissolve and thus release the drug substance when the intestinal pH reaches a value of 6.5 to 7.0, typically in the ileocaecal region. Although this is a well-established strategy, the drawback is that these coatings completely rely on the intestinal pH, which shows a high inter- and intra-subject variability, especially in patients with IBD conditions.
Time-controlled drug delivery systems, intended for colon targeting, release the drug over a prolonged time period and preferably exhibit a lag time before reaching the colon. However, these coatings are relying on the gastro-intestinal transit time which is again a high variable factor between subjects. Hence, these classical systems could result in a failure to deliver the drug as intended at the site of action.
To mitigate this risk and allow a more colon specific release, more advanced systems can be offered. These could be based on combining pH-triggered systems with other strategies, such as biodegradable polysaccharides. In that case, the dissolution of the coating is relying on two different mechanisms (pH and enzymatic degradation), which results in a lower failure rate, compared to the single pH-triggered systems.
In scope of colon targeting, a multiparticulate drug delivery system (such as mini-tablets and coated beads) is preferred over a monolithic system. The advantages of having a system where the dose is divided over multiple subunits are versatile: a lower risk of dose dumping, a more reproducible gastro-intestinal transit time, dose flexibility, the option to combine incompatible drugs, etc. Eurofins CDMO has the capabilities to encapsulate the minitablets or coated beads providing a convenient and patient-friendly final dosage form.
Solid biologics for Colon targeting
Biologics have revolutionized the treatment of various chronic diseases, offering targeted therapies with improved efficacy and safety. However, oral delivery of biologics remains a challenging task. In addition to obtaining suitable release characteristics, an extra challenge is to guarantee the chemical and physical stability of the biologic drug substance. The stability is crucial both in the solid dosage form and after release in the colon, where the biologic is often prone to enzymatic degradation. Eurofins CDMO has experience in the development of stable solid dosage forms for oral delivery of biologics to the colon. Techniques such as spray drying, freeze-drying, granulation and bead coating can be used as solidification process to convert the biologic in solution to a stable solid form.
Formulation screening and evaluation
Eurofins CDMO has different state-of-the-art coating techniques in-house (fluid bed coating, drum coating) to formulate coated drug products with a colon targeted release.
Suitable formulation strategies for either small molecules or biologics can be provided for pre-clinical and clinical testing.
In vitro tools are used to assess the release characteristics. Various dissolution set-ups are available in-house:
- USP I and II apparatus
- USP III apparatus
This allows testing of the formulations in buffers or biorelevant media during 1 or more stages.
Eurofins CDMO is committed to provide a dedicated team of technical experts involved from early development to clinical manufacturing ensuring a seamless transition from development to GMP.
Colon Targeting Network
Eurofins CDMO was part of the COLOTAN (Colon Targeting Network) consortium, which was a Training Network funded by the European Union, consisting of leading research groups from universities and from innovative pharmaceutical companies. The main objective was to improve targeting of oral drugs to the colon for effective treatment or colonic diseases.
Our PhD research is focusing on a formulation platform for the targeted delivery of biologics to the colon.
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