Encap Drug Delivery Introduces Colon-Screen
Product News Aug 19, 2011
Encap Drug Delivery, now offers a feasibility package that will evaluate the potential to use candidate compounds in formulations suitable for oral delivery to the colon.
This will involve the use of the Phloral™ coating technology developed by the London School of Pharmacy. This new technology represents a significant improvement in colonic delivery providing ‘fail-safe’ delivery of drug to the target site by employing two complimentary mechanisms to trigger drug release.
As well as a pH dependant coating it also incorporates a resistant starch component which is broken down specifically by the microbiota in the colonic region.
Recently colonic drug delivery has gained increased importance, not just for treatment of local diseases associated with the colon, e.g. Crohn's disease, ulcerative colitis, colorectal cancer and irritable bowel syndrome (IBS), but also for its potential as a site for the absorption of certain molecules due to the decreased levels of efflux transporters and membrane-bound metabolic enzymes known as cytochromes.
Its potential suitability for the oral delivery of peptides and proteins, oligonucleotides and vaccines is also an area of increasing interest.
Existing colonic systems generally involve coating the dosage unit with polymeric materials that will not normally dissolve in the low pH of the stomach or upper intestine but will dissolve in the higher pH of the lower intestine. Coatings that rely on a pH dependant system have the potential to be unreliable due to the large intra and inter patient variability in transit times and luminal pH.
The reliability of the new Phloral™ technology has been demonstrated in a recently published scintigraphic study in healthy volunteers (Ibekwe, Khela, Evans and Basit, Alimentary Phamacology & Therapeutics 28(7):911-6, 2008).
Dosage units with the combination coating all disintegrated in the colonic area as desired whereas many units coated exclusively with a commercially available pH coating passed through the gastrointestinal tract intact and failed to disintegrate.
One of the drawbacks to colonic delivery is the relatively low amount of water that is available for dissolution of dosage forms in this part of the gastrointestinal tract.
The combination of a reliable colonic targeting technology and the delivery of drugs in a liquid dosage form using Encap’s liquid fill technologies should provide a significant advance for the oral delivery of a wide range of drugs to the colon.
Encap now offers clients a feasibility package which will evaluate the potential to use candidate compounds in liquid fill formulations suitable for delivery to the colon. There are 4 stages to this screening process.
1) Prototype formulation evaluation
Studies are conducted to determine the feasibility of formulating the drug candidate in a stable dosage form. Prototype formulations are developed by incorporating the drug into vehicles that are suitable for liquid fill.
2) Assessment of the stability of the test compound to metabolism by colonic bacteria
The microbiota of the large intestine has the capacity to ferment or metabolize a large variety of molecules, which has implications for drug stability and may preclude colonic delivery for certain compounds. Drugs reaching the colon by virtue of poor solubility or the use of modified release dosage forms are particularly at risk. In this study, the candidate compound stability will be investigated in buffered faecal slurry which simulates the conditions of the lower gut.
3) Dissolution testing
Capsules are tested to ensure coating integrity and to predict in vivo drug release profiles for each prototype formulation. Prototype capsules must demonstrate resistance to the stomach, resistance to the upper GI tract and finally release the contents into colon.
4) PK study (Optional)
The Phloral coating is designed for use in the human colon, however it is recognized that clients may wish to generate preclinical data before progressing to human studies. In this optional study, the prototype formulation(s) will be administered to animals in a simple exploratory PK study. The data obtained will provide a quantitative measure of drug exposure in order to interpret preclinical efficacy.
This straightforward package of studies will allow companies to quickly test the suitability of delivering their compound to the colon as an oral dosage form.