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Colon - Targeted Drug Delivery System: A Review
Neeraj Sharma, P.K. Sharma, Nisha Mary Joseph and Mayank Bansal
KIET School of Pharmacy, Gaziabad (India)
ABSTRACT: Inflammatory2 bowel diseases including irritable bowl syndrome, ulcerative colitis and crohn’s disease are considered serious colonic disorder. Ulcerative colotis, if not treated, leads to colon cancer. More than 66,000 cases of colon cancer are reported to occur every year in India. Cancer of large intestine accounts for about 15% of cancer death in India. Oral delivery has become a widely accepted route of administration of therapeutic drug, the gastrointestinal3 tract present several formidable barrier to drug delivery. Colonic drug delivery is also found useful for improving systemic absorption of drug like nitrendipine, metoprolol, theophylline, isosorbide Mônonitrate.
KEYWORDS: Bowel Diseases, Gastrointestinal Tract, Isosorbide Mônnitrate, Metoprolol, Nitrendipine, Theophylline, Ulcerative Colitis
| Copy the following to cite this article: Sharma N, Sharma P. K, Joseph N. M, Bansal M. Colon - Targeted Drug Delivery System: A Review. Biosci Biotech Res Asia 2006;3(2a). |
| Copy the following to cite this URL: Sharma N, Sharma P. K, Joseph N. M, Bansal M. Colon - Targeted Drug Delivery System: A Review. Biosci Biotech Res Asia 2006;3(2a). Available from: https://bit.ly/3gk3lpu |
Introduction
4Factors to be Considered in The Design of Colon-Targeted Drug Delivery Systems
Anatomy and Physiology of Colon
Gastrointestinal Transit
The GI tract is divided into stomach, small intestine and large intestine. The large intestine extending from the ileocaecal junction to the anus is divided into three main parts. These are the6 colon, the rectum and the anal canal. The colon itself is made up of the caecum,the ascending colon, the hepatic flexure, the transverse colon, the splenic flexure, the descending colon and the sigmoidal colon.
pH in the Colon: Average8 pH in the GI tract
| Location | pH |
| Oral cavity | 6.2-7.4 |
| Oesophagus | 5.0-6.0 |
| Stomach | Fasted condation: 1.5-2.0
Fed condition: 3.0-5.0 |
| Small intestine | Jejunum: 5.0-6.5
Ileum: 6.0-7.5 |
| Large intestine | Right colon: 6.4
Mild and left colon: 6.0-7.4 |
The9 transit time of dosage forms in GI tract
| Organ | Transit time (hours) |
| Stomach | <1(Fasting)
>3(Fed) |
| Small intestine | 3-4 |
| Large intestine | 20-30 |
12Colonic Microflora
A large number of anaerobic and aerobic bacteria are present throughout the entire length of the human GI tract. The upper region of the GIT has a very small number of bacteria and predominantly consists of gram-positive facultative bacteria .The concentration of bacteria in the stomach is usually less then 103 colony-forming units/ml (CFU/ml) and most commomaly isolated species are streptococci, staphylococci, lactobacilli and various fungi. In the distal part of the small intestine, a higher concentration of anaerobic bacteria is found .The lower ileum has a bacteria concentration of 107-108 CFU/ml.The concentration of bacteria in the human colon is 1011-1112 CFU/ml.
Role of Absorption Enhancer
Absorption enhancers used in colonic drug delivery are
| Category | Agents |
| Nonsteroidal Anti-inflammatory agents | Indomethacine, Salicylates |
| Calcium ion chelating agent | Ethylenedimineteraacetic |
| Surfactants | Polyoxyethylenelaurylehter |
| Bile salts | Taurocholate, Glycocholate |
| Fatty acids | Sodium caprate, Sodium laurate |
5Pharmaceutical approaches to colon targeted drug drug delavery
| Approaches | Basic features |
| 1- Covalent linkage of a drug with a carrier | |
| 1.1 Azo conjugates | The drug is conjugated via an azo bond |
| 1.2 11Cyclodextrin conjugates | The drug is conjugated with Cyclodextrin |
| 1.3 Glycoside conjugates | The drug is conjugated with Glycoside |
| 1.4 Glucuronate conjugate | The drug is conjugated with Glucuronate |
| 1.5 Dextran conjugate | The drug is conjugated with dextran |
| 1.6 Polypeptide conjugate | The drug is conjugated with poly (aspartic acid) |
| 1.7 Polymeric prodrug | The drug is conjugated with polymer |
| 2- Approaches to deliver the intact molecule to colon | |
| 2.1 Coating with polymer | |
| 2.1.1 Coating with pH sensitive polymers | Formulation coated with enteric polymer releases drug when pH moves towards alkaline range |
| 2.1.2 Coating with biodegradable polymers | Drug is released by degradation of the polymer due to the action of colonic bacteria |
| 2.2 Embedding in matrices | |
| 2.2.1 Embedding in pH-sensitive matrices | Degradation of pH-sensitive polymer in GIT release the embedded drug |
| 2.3 Time release systems | Once the multicoated formulation passes the stomach, the drug is released after a lag time of 3-5hr.that is equivalent to small intestine transit time |
| 2.4 Redox-sensitive polymer | Drug formulated with disulfide polymer |
| 2.5 Bioadhesive systems | Drug coated with a bioadhesive polymer |
| 2.6 Coating with microparticles | Drug is linked with microparticles |
| 2.7 Osmotic controlled drug delivery | Drug is released due to osmotic pressure |
Evaluation of Colon –Targeted Drug Delivery System
Different in vitro and in vivo methods are used to evaluate the colonic drug delivery systems.
of colon-specific drug delivery system including rat (Van den Mooter et al., 1995; Leopold and Friend, 1995) and the pig (Harboe et al., 1989).
A-In Vitro Methods
The ability of the coats/carriers to remain for intact in the physiological environment of the stomach and small intestine is generally assessed by conducting drug release studies in 0.1N HCL for 2 hrs. (Mean gastric emptying time) and in pH 7.4 Sorensen’s phosphate buffer for 3 hrs.(mean small intestine transit time) using USP 1dissolution rate test apparatus or flow through dissolution apparatus.
B- In Vivo Methods
Different animal models are used for evaluating in vivo performance of colon-specific drug delivery systems. Guinea pigs were used to evaluate colon-specific drug delivery from a glycoside prodrug of dexamethasone (Friend et al., 1991). Other animal models used for the in vivo evaluation of colon-specific drug delivery system including rat (Van den Mooter et al., 1995; Leopold and Friend, 1995) and the pig (Harboe et al., 1989).
In vivo Technique
The in vivo techniques are
String Technique
Endoscope Technique
Radio telemetry
Roentgenography
Gamma scintigraphy
Conclusions
A considerable amount of research work has been carried out on the development of colon-specific drug delivery system for the last two decades. The advantages of targeting drug specifically to the diseased colon are reduced incidence of systemic side effects, lower dose of drug, supply of the drug to the biophase only when it is required and maintenance of the drug in its intact from as close as possible to target site.
References
- The United State Pharmacopeia, Asian ed.; (2003).
- Triphati, K.D., Essential of Medical Pharmacology; Jaypree Brothers Medical Publishers (P) Ltd, 437 (2004).
- Martindale ‘The Complete drug Reference’, 30th ed.; 1136.
- Jain, N.K.; Advances in controlled & Novel Drug Delivery, CBS Publishers, 89 (2005).
- Chourasia, M.K. and Jain, S.K., Pharmaceutical approaches to colon targeted drug delivery system; Dr.Hari Singh Gour University, Sagar.
- Colon-specific drug delivery system. J. Pharma. Sci, 62: 1-8 (2000).
- Colonic transit of different sized tablets in healthy subjects. Control Rel., 26:
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