The enzymatic activities associated with the micro flora of colon can be used as a tool for colon specific drug delivery. The large intestine has been appreciated as a promising site for the administration of poorly absorbable drug molecules for their improved bioavailability following oral administration. The colon is known to have somewhat lesser diversity and intensity of enzymatic activities as compared to stomach and small intestine. In addition, the colon has a longer retention time and appears to be highly responsive to agents that enhance the absorption of poorly absorbed drugs.
The site-specific delivery of drugs to the colon has implications in a number of areas which include-
Local treatment and irradication of colonic diseases.
For delivering peptides and proteins through oral route (colon targeted products).
In the improvement of therapy in diseases susceptible to diurnal rhythm.
Colonic delivery system-
The system designed for the delivery of drug in the colon may be of single or a multiple unit dosage form, which is based on the core being coated with one or more successive layers. Such a system may be composed of the following-
- An outer film, which recognizes if the system has left the stomach.
- An intermediate layer which swells (based on hydrophilic swellable polymer) following the outer film, which dissolves in the small intestine. This layer has to protect the core during the small intestine transit (at least 3-4 hours).
- An additional layer between the swellable polymer and core is casted in order to deter premature release of contents.
- The core containing the drug which may be released promptly or in a sustained/ prolonged pattern.
Factors affecting drug absorption from the colon-
- Delivery rate to colon
- Lipid solubility
- Colonic residence, site of absorption in colon (proximal or distal)
- pH / pKa of drug
- Micro flora climate of colon
- Mucous barrier
- Mucosal pore size and permeability index
- Concentration of drug Vs colon contents
In vitro models to assess colonic biotransformation-
To understand colonic drug disposition in vivo, following in vitro models are devised-
-Studies with colonic tissues including colonic slices, segments, isolated mucosa, human colonic organ culture.
- Studies with cellular preparations
-Studies with sub cellular preparations viz. using coenzyme, cell fractionation isolate mitochondria and studying metabolism kinetics
Methods of studying colonic drug absorption-
- Radiolabeling: gamma scintigraphy or neutron activation analysis.
- Gamma camera imaging.
- Telemeric capsule.
- Colonoscopy.
- Artificial stroma.
List of representative peptide and protein drugs and their potential functions and biomedical applications is available. Interested parties are advised to please contact me at 1-514-743-6159 or email at drshrutibhat@gmail.com.
For additional reading on mucosal DDS, in my next chapter, I shall present a list of references that may be useful to give more insight into this delightful topic.
For an expert opinion on formulation development of peptide/ protein molecules http://www.drshrutibhat.com
My other blog that might be of interest- http://www.qa-expert.com/
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