When drugs are bioavailable in blood circulation, they reach every part of the body and cause undesirable side effects. Novel drug delivery ensures that maximum therapeutic efficacy can be obtained with minimum side effects. Targeted drug delivery to various parts of the human body is a part of novel drug delivery which ensures that the drug is available at the site of disease and minimum quantity is in circulation reaching undesirable tissues and organs, thus, minimizing side effects. Drug delivery targeting various parts of the gastrointestinal tract (git) is achieved utilizing various targeting approaches relevant to the concerned part of the git.
Colon targeted drug delivery systems are specially developed to target diseases of the colon, like ulcerative colitis, chron’s disease, irritable bowel syndrome or colon cancer. Such delivery systems aim for local delivery at the site of disease with minimum systemic absorption. The colon or the large intestine is the terminal part of the git ending with the anus. The colonic fluids are viscous harbouring a diverse microbial flora which is not seen in the upper parts of the git. The pH of the colon is on the alkaline side, usually greater than 6.5, however, inter subject variations are also seen which make the development of formulations more challenging.
Several colon targeting approaches have been devised accordingly for delivery of drugs in the colonic part of the git, as follows:
- pH dependent approach
We are aware that the git has variations of pH ranging from highly acidic to alkaline. The stomach pH of the human body generally ranges from 1-2; whereas the pH gradually rises as we cross the duodenum, jejunum and ileum, the three parts of the small intestine. The pH in the small intestine may range from 4.5 to 7.5 or greater. Finally the pH of the colon usually ranges from 6.5 to 7.5. However, higher and lower ranges have also been observed. Keeping these considerations in mind, dosage forms have been prepared or coated with polymers that are soluble in higher pH, greater than pH 6 or 7 (like shellac, Eudragits, Cellulose acetate phthalate, etc) which are resistant to pH in the upper parts of git including the stomach and major part of the small intestine. The drug release starts to occur once the pH is near to neutral and thus, minimum drug release occurs in the upper git including the small intestine and major amounts of release occurs in the colon.
- Time dependent release
Like the pH, the transit times of food or drugs in various parts of the git is an important factor which can be considered when developing strategies for colon targeting. Usually, the gastric transit time ranges from 15 min to 2 hours and the transit time in small intestine is approximately 3 hours. Thus, 5 hours of time on average is required for a dosage form to cross the upper parts of the git and to reach the large intestine. With this observation, we can develop dosage forms with high molecular weight polymers (like Hydroxypropylmethylcellulose, Carbopol, Ethylcellulose, etc) or hydrogels (alginate, pectin, etc) which have crosslinked structures and release drug slowly by diffusion. The concentration of the polymer can be optimized in such a way that the drug release starts approximately after 5 hours and then sustained release of the drug occurs in the colon. The residence time of a particular dosage form is much higher than that of stomach or small intestine and ranges from 2-48 hours. Thus, enough time for the sustained drug release is there in the colon. Further, small amounts of release over prolonged periods of time allow the drug to act over the whole length of the colon and allow dissolution in the small volume of colonic fluids. The viscous fluid in the colon is present in small pockets spread over the entire length of the colon, rather than filling the whole lumen. Thus sustained release of drug is highly favourable. Further, fast release from the dosage form may cause exposure of the colonic mucosa to high concentrations of drug resulting in irritation.
- Microbial triggered systems: degradation of natural polysaccharides
This approach is perhaps is one of the most researched topics which has attracted the interests of the formulation scientists recently. Natural polysaccharides like alginate, chitosan, pectin, inulin, natural gums like xanthan or gellan, have been explored extensively. The colon is the site which harbours maximum concentrations of microbial flora in the git and they secrete enzymes which can degrade and break down the natural polysaccharides. Scarce amounts of microbial flora in the highly acidic environment of stomach or in alkaline small intestine cause the dosage forms prepared with such polysaccharides to pass the upper git without releasing any drug. However, in the colonic environment when the enzymes degrade and break down the polysaccharides, the drug release occurs. Such polymers being biodegradable are also safe and nontoxic compared to synthetic polymers used in earlier approaches.
Apart from these, osmotic drug delivery has been used in colon targeting which is neither dependent on pH, transit times or microbial flora. They release drug due to generation of osmotic pressure within the device.
Colon targeting is one of the most promising prospects for treatment and management of colonic diseases. However, the formulation challenges need to be solved with brainstorming strategies which can deliver maximum amounts of drugs to the colon causing lesser side effects. Certain important approaches are hereby outlined which may help to overcome the challenges and ensure better therapeutic effect for the consumers, which is the ultimate goal for every researcher involved with formulation development.
References:
- Das M, Ghosh LK. Colon Targeting Of Drugs: The Factors, Targeting Approaches And Evaluation Strategies. International Journal of Pharm Tech Research, Vol.5, No.3, 2013, pp 1416-1425.
- Das M, Ghosh B, Sen S and Ghosh LK. Formulation and Optimization of Controlled Release 5-Fluorouracil Tablets for Colonic Delivery. J Young Pharm. Vol. 9(2), 2017, pp 192-196.
- Yihong Qiu, Yisheng Chen, Geoff G.Z. Zhang. Developing solid oral dosage forms: Pharmaceutical Theory and Practice, 2009, Pg 283
- Hong Wen, Kinam Park, Oral Controlled release formulation design and drug delivery, 2010, pg 3
