COLON SPECIFIC DRUG DELIVERY SYSTEM:
The most convenient route for the administration of drugs to the patients is oral route. When the conventional dosage forms are administered orally they dissolve in the stomach fluid or intestinal fluid and depend upon the physicochemical properties of the drug they get absorbed from the regions of the GIT. It is considered as a serious drawback in conditions where localized delivery of the drugs in the colon is required or in conditions where a drug needs to be protected from the intimidating environment of upper GIT. So, the dosage forms that deliver drugs into the colon rather than upper GIT prefers number of advantages as shown in Figure 1.1.
The CDDS is capable of protecting the drug release and absorption of drugs from the stomach as well as the small intestine. It will also protect the degradation of bioactive agent from both of the dissolution sites and made them to release and absorb once the system reaches the colon. Targeted drug delivery into the colon is highly desirable for local treatment of a variety of bowel diseases such as ulcerative colitis, Crohn's disease, amoebiasis, colonic cancer, local treatment of colonic pathologies, and systemic delivery of protein and peptide drugs.
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The most preferred route for CDDS is oral route. But some other routes may be used. Rectal administration offers the shortest route for targeting drugs to the colon. However, it is difficult to reach the proximal part of colon via rectal administration. Rectal administration can also be uncomfortable for patients and compliance may be less than optimal. Drugs can be supplied as solutions, foam, and suppositories for intrarectal administration. The intrarectal route is used for both systemic dosing and for the delivery of topically active drug to the large intestine.
The colonic contents are significantly viscous and their mixing is not efficient, due to its high water absorption capacity of the colon, thus the accessibility of most drugs to the absorptive membrane is low. The human colon has over 400 distinct species of bacteria as resident flora, a possible population of up to 1010 bacteria per gram of colonic contents. Among the reactions carried out by these gut flora are azoreduction and enzymatic cleavage i.e. glycosides. These metabolic processes may be responsible for the metabolism of many drugs and may also be applied to colon-targeted delivery of peptide based macromolecules such as insulin by oral administration.
Advantages: (Anil K. Philip., et al., 2010)
Drugs that are destroyed by the acidic environment of the stomach or metabolized by pancreatic enzymes are only slightly affected in the colon.
Sustained colonic delivery of the drugs can be useful in conditions in which diurnal rhythm is evident like nocturnal asthma, angina and arthritis.
Treatment of Ulcerative colitis, Crohn's disease, Amoebiasis and colorectal cancer is more effective with the direct Delivery of the drugs to the colon.
The features of the colon that makes it suitable targeting various drugs including proteins and peptides are
Its lower metabolic activities.
Longer residence time (20-30 hrs).
Responsiveness to absorption enhancers.
Targeting opportunities offered by colonic bacterial enzymes.
Trans mucosal and membrane potential difference that is significant in the
absorption of the ionized and unionized drugs.
Possibility that bulk water absorption in this region may provide scope for solvent
Criteria for Selection of Drug for CDDS:
The colon is a good site for the absorption of drugs that are not stable in the acidic environment of the stomach, cause gastric irritation (e.g. aspirin, iron supplements) or those degraded by small intestine enzymes. There number of drugs is available as sustained released or delayed release or time-release tablets for oral administration. The different categories of the drugs that are available in this form are NSAIDs; anti-hypertensive drugs etc. There will be in question when these drugs do not have good absorption characteristics in the colon and it leads to improper management of respective disorders through sustained released or time released formulations. This is due to the fact that most formulations are supposed to release their drug slowly over a period of 12 hrs or 24hrs. The total residence time of these formulations in the stomach and small intestine will not be more than 5-6 hrs. If the drug is not having inherent absorption properties from the colon it will be eliminated in the feces as it is.
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The diseases such as Amoebiasis require selective local delivery of drugs to the colon. Colonic drug delivery can be achieved by oral or by rectal administration. Conventional rectal delivery forms are not always effective because of high variability is observed in the distribution of drugs administered by this route. Suppositories are effective in the rectum because of the confined spread and enema solution can only be applied topically to treat disorders of the sigmoid and descending colon. Therefore, the oral route is preferred. Absorption and degradation is the major obstacle with the delivery of drugs by the oral route and must be overcome for successful colonic drug delivery.
Figure 1.1 The Comparative Study Colon Targeted Dosage Form with Conventional Dosage Form
The drug Tinidazole was selected for CDDS because, the administration of Tinidazole by conventional tablet dosage form provides minimal amount of drug for local action in the colon, because the absorbitivity of Tinidazole through whole GIT is good. So, to prevent its absorption from stomach, small intestine, avoid systemic effects and increasing the availability of drug for local action the delivery of the drug in colon was selected.
STRUCTURE AND FUNCTION OF COLON:
The large intestine extends from the ileocecal junction to anus and it is divided into 3 main parts namely colon, rectum, and anal canal respectively. The Anatomical and physiological characteristics of the GIT were shown in Table 1.1. The colon part consists of the cecum, ascending colon, hepatic flexure, transverse colon, descending colon, and sigmoid colon. It has been shown in Figure 1.2. Cecum is the widest part of the colon and it is approximately 8.5 cm long.
The main functions of colon are,
To absorb fluids and the salts that remains after the completion of intestinal digestion.
To mix its contents with mucus for lubrication.
The ascending colon is extends from the cecum to the hepatic flexure and its approximately 20 cm long, which lies lateral to the right kidney and in contact with the inferior Surface of the liver. The transverse colon is hangs loosely between the hepatic and the splenic flexures which is normally 45 cm in length. The splenic flexure is typically located higher than the hepatic flexure. The descending colon extends downwards from the splenic flexure to the pelvic brim and is approximately 30 cm long. The colon then turns towards the midline to form the 40 cm coiled sigmoid colon.
Table 1.1 Anatomical and Physiological Characteristics of the Gastrointestinal Tract
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Figure 1.2 Anatomy of Colon
COLONIC MICRO FLORA:
The GIT is sterile at birth, but colonization typically begins within a few hours of birth, starting in small intestine and progressing caudally over the period of several days.
Slow movement of material through the colon allows a large microbial Population to flourish there. The upper region of the GIT has a very small number of bacteria (103 CFU/ml). Under normal conditions, the micro flora of the proximal small bowel is similar to those of the stomach, the bacterial concentration being 103-104 CFU/ml. The lower and the distal ileum have a bacterial concentration of 106-107 CFU/ml. In the ileocecal sphincter, the bacterial concentration increases dramatically. The concentration of bacteria in the human colon is 1011-1012CFU/ml11. It has been shown in Table 1.1. The bacterial micro flora is predominantly anaerobic, some aerobic species and is composed of more than 400 strains, like of Bacteroides, Eubacteria, Clostridia, Enterococci, Enterobacteria, and Ruminococcus etc. These bacterial micro floras will degrade various polysaccharides and which has been listed in Table 1.2.
The anaerobic outnumber the aerobic by a factor of 103-104. Approximately 30% of the dry weight of the feces consists of bacteria. Carbohydrates that enter the colon are fermented by the colonic bacteria, polysaccharides and glycosidases enzymes to short chain fatty acids mainly acetic acid, prop ionic acid, and butyric acid; carbon dioxide (CO2), hydrogen (H2), methane (CH4) and hydrogen disulfide (H2S). For fermentation the micro flora produces vast number of enzymes like Î²-glucoronidase, Î²-xylosidase, Î² - galactosidase, Î±-arabinosidase, nitroreductase, and azoreducatase, deaminase, and urea dehydroxylase.
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Table 1.2 Bacterial Species Involved in the Degradation of Various Polysaccharides
Galactomannan (Guar Gum )
Bacteroides, bifidobacteria, Ruminococci
Bacteroides, bifidobacteria, Eubacteria
DRUG ABSORPTION IN THE COLON:
In colon the drugs are absorbed passively through paracellular and transcellular routes which have been shown in Figure 1.3. Transcellular absorption involves the transport of drugs through the firm junctions between the cells and most of the lipophilic drugs take this route, whereas hydrophilic drugs rather absorb through paracellular route. Studies in rat have indicated that paracellular absorption is constant through the small intestine, but transcellular absorption appears to be restricted to the small intestine, with trifling colonic absorption by this route. The poor paracellular absorption of many drugs in the colon is due to fact that the epithelial cell junctions are very tight. The slow rate of transit in colon makes it possible for the drug to stay in contact with mucosa for a longer period than in small intestine which compensates the much lower surface areas. The colonic contents become more viscous with progressive absorption of water as one travels further through the colon. This causes a reduced dissolution, and slow diffusion of dissolved drug through the mucosa. Because of the small extent of paracellular transport, the colon is a more selective site for drug absorption than the small intestine.
Figure 1.3 Drug Absorption through Colon
PRIMARY APPROACHES FOR CDDS: (Chourasia M.K., et.al., 2003)
Table 1.3 Different Approaches for CDDS
The drug is conjugated via an azo bond
The drug is conjugated with Cyclodextrin
The drug is conjugated with glycoside
The drug is conjugated with Glucuronide
The drug is conjugated with dextran
The drug is conjugated with polypeptide
The drug is conjugated with polymer
Coating with polymer
Coating with pH sensitive
Formulation coated with enteric polymers release drug
when pH moves towards alkaline range
Drug is released following degradation of the polymer
due to the action of colonic bacteria
Embedding in matrices
The embedded drug in polysaccharide matrices is
released by swelling and biodegradable action of
Embedding in pH
Degradation of pH sensitive polymer in the GIT releases the embedded drug
TIMED RELEASED SYSTEMS
Redox sensitive system
Drug coated with Bioadhesive polymer that selectively provides adhesion to colonic mucosa.
Coating of miroparticles
Drug is released through semi permeable membrane
pH Sensitive Polymer Coated Drug Delivery to the Colon:
Table 1.4 Threshold pH of Commonly used Polymers for Coating
Eudragit L 100
Eudragit S 100
Eudragit L 30 D
Eudragit FS 30 D
Eudragit L 100-55
Polyvinyl acetate phthalate
Hydroxy propyl ethyl cellulose phthalate
Hydroxy propyl ethyl cellulose phthalate 50
Hydroxy propyl ethyl cellulose phthalate 55
Cellulose acetate trimelliate
Cellulose acetate phthalate
In the stomach, pH ranges between 1 and 2 during fasting but the pH increases after eating. The pH is about 6.5 in the proximal part of small intestine and about 7.5 in the distal part of small intestine. The pH declines significantly from the ileum to the colon. It is about 6.4 in the cecum. However, pH values as low as 5.7 have been measured in the ascending colon in healthy volunteers. The pH in the transverse colon is 6.6 and 7.0 in the descending colon. Use of pH dependent polymers is based on these differences in pH levels which have been shown in Table 1.4. The polymers described as pH dependent in colon specific drug delivery are insoluble at low pH levels but become increasingly soluble as pH rises. Although a pH dependent polymer can protect a formulation in the stomach, and proximal small intestine, it may start to dissolve in the lower small intestine, and the site-specificity of formulations can be poor. The decline in pH from the end of the small intestine to the colon can also result in problems, lengthy lag times at the ileocecal junction or rapid transit through the ascending colon which can also result in poor site-specificity of enteric-coated single unit formulations.
Delayed (Time) Release Drug Delivery to Colon:
(Anil K. Philip., et al., 2010)
Time controlled release system (TCRS) such as sustained or a delayed release dosage forms are also very promising drug release systems. The mode of action is shown in Figure 1.4. However, these may show the bioavailability changes due to variations of gastric emptying time of dosage form (in humans) so, the arrival time of dosage form to colon cannot be accurately predicted. Even though these dosage forms use as colon targeting dosage forms by prolonging their lag time about 5 to 6 h. The disadvantages of this system are as follows:
i. varying of the gastric emptying time between subjects, type of food and amount of food intake.
ii. Motility of gastro intestine, in that especially peristalsis or contraction movement in the stomach causes in change of GI transit time of the dosage form/ drug.
iii. Presence of disease may change the GI transit time for example accelerated transit of the colon has been observed in patients with the IBD, carcinoid syndrome, diarrhea, and the ulcerative colitis.
Due to the above reasons, the time dependent systems are not ideal to deliver drugs to the colon (specifically for the treatment of colon related diseases). Proper combination of pH sensitive and time release dosage forms functions into a single dosage form may get better site specificity of drug delivery to the colon. Since the transit time of dosage forms in the small intestine is less variable i.e. about 3Â±1 h the time-release function (or timer function) dosage forms should work more efficiently in the small intestine when compared to the stomach. The working of this dosage forms are as follows:
Drug carrier will deliver the drug to target site in the small intestine. The drug release will produce after a predetermined time point subsequent to gastric emptying. Drug release from these systems should be suppressed by a pH sensing function i.e. acid resistance of the dosage form, which would decrease gastric residence time variations. When the dosage form crosses the stomach, the enteric coating layer given to dosage form rapidly dissolves and the intestinal fluid begins to slowly erode the press coated polymer (HPC) layer. When the erosion front reaches the core tablet, rapid drug release occurs since the erosion process takes a long time as there is no drug release period (lag phase) after gastric emptying. The period of lag phase is restricted either by the change in weight or composition of the polymer (HPC) layer.
Figure 1.4 Release of Drug from Delayed Release Drug Delivery
Microbially Triggered Drug Delivery to Colon:
(Sinha V.R., et al., 2003)
The microflora present in the colonic region is ranges from 1011 -1012 CFU/ ml. the flora mainly consists of anaerobic bacteria like bacteroides, bifidobacteria, eubacteria, clostridia, enterococci, enterobacteria and ruminococcus etc. The bacterial colonies that present in colon gets its energy by fermenting various types of substrates that have been left undigested in the small intestine like di- and tri-saccharides, polysaccharides etc. For the energy process (fermentation), the bacteria present in flora produces a numerous enzymes. Those are like glucoronidase, xylosidase, arabinosidase, galactosidase, nitroreductase, azareducatase, deaminase, and urea dehydroxylase. Because of presence of these enzymes the biodegradable polymers can serve as major excipients in the preparation of the dosagefroms that serve the release of drug in the colon. So, the use of biodegradable polymers for colon-specific drug delivery seems to be a more site-specific approach as compared to other approaches. These polymers safeguard the drug from the environments of stomach and small intestine, and are capable to deliver the drug to the colon. On reaching the colon, they undergo incorporation by micro-organism, or degradation by enzyme or break down of the polymer back bone leading to a subsequent reduction in their molecular weight and thereby loss of mechanical strength. They are then unable to hold the drug entity any longer.
Prodrug Approach for Drug Delivery to Colon: (Jose S., et al., 2010)
Prodrug is a pharmacologically inactive derivative of a parent drug molecule that requires spontaneous or enzymatic transformation to release the active drug. Prodrug is designed for colonic delivery, which undergoes minimal hydrolysis in the upper part of GIT, and releasing the active drug moiety from the drug carrier by undergoes enzymatic hydrolysis in the colon. Limitations of the Prodrug approach are that it is not a very adaptable approach as its formulation depends upon the functional group available on the drug moiety for chemical linkage. Furthermore, prodrugs are new chemical entities, and need a lot of evaluation before being used as carriers.
In some newer approaches polymers are used as drug carriers for drug delivery to the colon. Both synthetic as well as naturally occurring polymers have been used for this rationale. Some of the sub synthetic polymers have been used to form polymeric Prodrug with azo linkage between the drug moiety and polymer. Various azo polymers have also been evaluated as coating materials over drug cores. These have been found to be equally vulnerable to cleavage by the azoreducatase in the large intestine. Coating of peptide capsules with polymers cross linked with azoaromatic group has been found to protect the drug from digestion in the stomach and small intestine. In the colon, the drug is released by reducing azo bonds.
Polysaccharide Based Delivery Systems: (Libo Yang., et al., 2002)
Polysaccharides are naturally occurring polymers, attracting a lot of attention for targeting the colon. Since these polymers are monosaccharides and are found in plenty, have ample availability, inexpensive and are available in a verity of a structures with varied properties. We can modify easily the chemical, biochemical properties of these polymers. These Polysaccharides are highly stable, safe, nontoxic, hydrophilic, gel forming and in addition, they are biodegradable. These include naturally occurring polysaccharides from plants like guar gum, inulin, polysaccharides obtained from animals such as chitosan, chondrotin sulphate, polysaccharides obtained from algal like alginates or obtained from microbial origin such as dextran. The polysaccrides can be broken down by the colonic microflora to simple saccharides. Therefore, they fall into the category of "Generally Regarded As Safe" (GRAS).
Newly Developed Approaches for CDDS: (Anil K. Philip., et al., 2010)
Pressure Controlled Drug-Delivery Systems:
As a result of peristalsis, higher pressures are encountered in the colon than in the small intestine. Based on this pressure controlled colon-delivery capsules were prepared using ethyl cellulose, which is insoluble in water. In such systems, disintegration of a water-insoluble polymer capsule occurs because of pressure in the lumen of the colon following this drug release occurs. For the disintegration of the formulation the thickness of the ethyl cellulose membrane is the most important factor. The system furthermore appeared to be depending on capsule size and density. Due to the reabsorption of water from the colon, the viscosity of luminal content is higher in the colon than in the small intestine. It has consequently been concluded that drug dissolution in the colon could present a problem in relation to colon-specific oral drug delivery systems. In pressure controlled ethyl cellulose single unit capsules the drug is in a liquid. When pressure-controlled capsules were administered to humans lag times of three to five hours in relation to drug absorption were noted.
Novel Colon Targeted Delivery System (CODESTM):
CODESTM is a unique CDDS technology, shown in Figure 1.5 was designed to avoid the inherent problems associated with pH or time dependent systems. CODESTM is a combined approach of pH dependent and microbially triggered CDDS. It has been developed by utilizing a unique mechanism involving lactulose, which acts as a trigger for site specific drug release in the colon. The system consists of a traditional tablet core containing lactulose, which is over coated with an acid soluble material, Eudragit E, and then subsequently over coated with an enteric material, Eudragit L. The premise of the technology is that the enteric coating protects the tablet while it is located in the stomach and then dissolves quickly following gastric emptying. The acid soluble material coating then protects the preparation as it passes through the alkaline pH of the small intestine. Once the tablet arrives in the colon, the bacteria enzymetically degrade the polysaccharide (lactulose) into organic acid. This lowers the pH surrounding the system sufficient to affect the dissolution of the acid soluble coating and subsequent drug release.
Figure 1.5 Release of Drug from CODESTM
Osmotic Controlled Drug Delivery (ORDS-CT):
(Rajan K. Verma., et al., 2002)
The OROS-CT (Alza Corporation) can be used to target the drug locally to the colon for the treatment of disease or to achieve systemic absorption that is otherwise unattainable. The OROS-CT system can be a single osmotic unit or may incorporate as many as 5-6 push-pull units, each 4 mm in diameter, encapsulated within a hard gelatin capsule. Each bilayer push pull unit contains an osmotic push layer and a drug layer, both surrounded by a semi permeable membrane. An orifice is drilled through the membrane next to the drug layer. Immediately after the OROS-CT is swallowed, the gelatin capsule containing the push-pull units dissolves. Because of its drug-impermeable enteric coating, each push-pull unit is prevented from absorbing water in the acidic aqueous environment of the stomach, and hence no drug is delivered. As the unit enters the small intestine, the coating dissolves in this higher pH environment (pH >7), water enters the unit, causing the osmotic push compartment to swell, and concomitantly creates a flowable gel in the drug compartment. Swelling of the osmotic push compartment forces drug gel out of the orifice at a rate precisely controlled by the rate of water transport through the semi permeable membrane. For treating ulcerative colitis, each push pull unit is designed with a 3-4 h post gastric delay to prevent drug delivery in the small intestine. Drug release begins when the unit reaches the colon. OROS-CT units can maintain a constant release rate for up to 24 hours in the colon or can deliver drug over a period as short as four hours. Recently, new phase transited systems have come which promise to be a good tool for targeting drugs to the colon. Various in vitro / in vivo evaluation techniques have been developed and proposed to test the performance and stability of CDDS.
Formulation Factors Affecting Drug Release from ODDS:
The various formulation factors affecting the drug release from ODDS are listed below in Table 1.5.
Table 1.5 Formulation Factors Affecting Drug Release from ODDS
Release rate directly proportional to the solubility of drug within the core. Both highly and poorly water soluble drugs are not good candidates for osmotic delivery. Number of approaches available to deliver drugs having extremes of solubility.
Release rate directly proportional to the osmotic pressure of the core formulation. Additional osmogent required if drug does not possess suitable Osmotic pressure.
Should be within the desired range to control the drug release. Number of approaches available to create orifice within the membrane.
Release rate affected by the type and nature of membrane forming polymer, thickness of the membrane, and presence of other additives (type and nature of plasticizer, flux additives, etc.). Membrane permeability can be increased or decreased by proper choice of membrane-forming polymers and other additives.
Compounds that can be used as Osmogents:
Compounds that can be used as osmogents in Osmotic drug delivery system were listed in the Table 1.6.
Table 1.6 List of Osmogents used in ODDS
Water-soluble salts of inorganic acids
Magnesium chloride or sulfate; lithium, sodium, or potassium chloride; lithium, sodium, or potassium sulfate; sodium or potassium hydrogen phosphate, etc.
of organic acids
Sodium and potassium acetate, magnesium succinate, sodium benzoate, sodium citrate, sodium ascorbate, etc.
Arabinose, ribose, xylose, glucose, fructose, galactose, mannose, sucrose, maltose, lactose, raffinose, etc.
Water-soluble amino acids
Glycine, leucine, alanine, methionine, etc.
Organic polymeric osmogent
Sodium carboxyl methylcellulose, HPMC, hydroxyethyl methylcellulose, cross-linked PVP, polyethylene oxide, carbopols, polyacrylamides, etc.
Microbially Activated Osmotic Drug Delivery System (MAODS):
(Navnit Hargovindas Shah., et al., 2000)
MAODS used for targeting drugs to the colon, which is shown in Figure 1.6. The drug delivery system of this invention is a tablet comprising of three parts,
An inner core comprising a swelling agent and an active ingredient.
A central semi permeable polymer membrane containing a plasticizer.
An outer enteric coating.
The three parts of this system function to provide for release of drug to the colon without premature delivery of drug to the upper GIT. The outer enteric coat, being resistant to the acidic gastric environment, keeps the tablet intact until the tablet reaches the small intestine, the outer enteric coating dissolves allowing for gastrointestinal fluid to diffuse through the semi permeable membrane into the core. No drug is released in this time. The core swells as a result of penetration of gastrointestinal fluid during the transit of the tablet through the small intestine. Finally, after a consistent period of 4-6 hours transit in the small intestine, the swollen core bursts the semi permeable membrane releasing the active ingredient in the colon.
The core contains an active ingredients in a pharmaceutical acceptable carrier mixed with a swelling agent and various other pharmaceutically acceptable excipients, such as binders, lubricants or binders. The swelling agent may be a disintegrating agent, synthesized polymers and osmotic agents. The core of the delivery system is prepared by any conventional means. Preferably, the core is prepared by using wet granulation and compressed into tablets by conventional means. The membrane coating of the invention is a semi permeable polymer membrane. This semi permeable membrane allows water influx but prevents outward
Figure 1.6 Release of Drug from MAODS
diffusion of drug. Any polymer material having such properties may use accordance with the invention. Along with this semi permeable polymer any conventional plasticizer was used. The semi permeable membrane may be applied to the core using any conventional coating system.
The outer coating consists of any conventional acid resistant enteric coating material. The enteric coating may be applied to the core encased by the semi permeable membrane by any conventional means.
ROLE OF BIODEGRADABLE POLYSACCHARIDES IN COLON TARGETED DRUG DELIVERY: (Das D., et al., 2003;Ravi V., et al., 2008)
Polysaccharides preserve their integrity because they are resistant to the digestive action of gastrointestinal enzymes. The matrices of polysaccharides are assumed to remain intact in the physiological surroundings of stomach and small intestine, but once they reach in the colon, they are acted upon by the bacterial polysaccharidases and result in the degradation of the matrices. The family of natural polymers has an appeal to the area of drug delivery as it is comprised of polymers with a large number of derivatizable groups a wide range of molecular weights, varying chemical compositions and for the most part, a low toxicity and biodegradability, yet a high stability. The most favorable property of these materials is that they are already approved as pharmaceutical excipients. A problem encountered with the use of polysaccharides is their high water solubility. An ideal approach is to modify the solubility while still retaining their biodegradability. Large numbers of polysaccharides have already been tried for their potential as colon-specific drug carrier systems, as shown in the table 1.7.
Table 1.7 List of Biodegradable Polysaccharides in Colon Targeted Drug Delivery
Composed of D galactose & 3,6- anhydro-D-galactose, with sulfate ester groups on both sugar components
Sea weed extract
Î¬ -1,6 D-glucose
Plant seed endosperm of the seeds of cyamopsis
Used in food industry as thickening agent, degraded by Bacteroides, Ruminococcus
random copolymer of
(1-4) linked Î² D
mannose & Î²-D glucose
used as drug carrier, enzyme
entrapment, reduces cholesterol level
D-glucose, D glucoronic
acid & rhamnose in Î²-1,4 linkage
D- glucoronic acid and N-acetyl glucosamine in Î²-1,3 and Î²-1,4 linkage, linear
Human and animal (intercellular
material in the
skin, cartilage and muscle)
(sterculia gum, Indian
Mixture of D-galactose, L-rhamnose and D galctouronic
The galctouronic acid units are the branching points of the molecule
Locust bean gum
it requires heat to achieve full hydration and maximum viscosity
(1â†’3)-linked Î²- D galactopyranosyl units
At every third unit it bears a single Î²-Dglucopyranosyl
Unit linked (1â†’6)
Used widely in industry, used for laxative, antitumor, antimicrobial
Maltotriose in - Î¬ (1,4)
Linkage connected by
Plant cell walls
Most abundant hemicellulose,
degraded by Bacteroides,
AMOEBIASIS: (Samuel L. Stanley., et al., 2003)
Amoebiasis is the world's second leading cause of death from parasitic disease. The causative protozoan parasite, Entamoeba histolytica, is a potent pathogen which has been shown in the Figure 1.7, which secretes proteinases that dissolve host tissues, killing host cells on contact, and engulfing RBCs, E histolytica trophozoites assault the intestinal mucosa, causing amoebic colitis. In some cases E histolytica breach the mucosal barrier and travel through the portal circulation to the liver, where they cause abscesses which consists of few E histolytica trophozoites surrounding dead and dying hepatocytes and liquefied cellular debris. Amoebic liver abscesses grow unavoidably and, at one time, were almost always fatal, but now even large abscesses can be cured by one dose of antibiotic. Evidence that what we thought was a single species based on morphology is, in fact, two genetically distinct species now termed Entamoeba histolytica and Entamoeba dispar has turned conventional perception about the epidemiology and diagnosis amoebiasis upside down. New models of disease have linked E histolytica stimulation of intestinal inflammation and hepatocytes programmed cell death to the pathogenesis of amoebic colitis and amoebic liver abscess. The various drugs used for the treatment of Amoebiasis were listed in the Table 1.8.
Figure 1.7 E histolytica in Stools
Table 1.8 List of Drugs used in the Treatment of Amoebiasis
Activated in anaerobic organisms by reduction of 5-nitro group. Activated compound damages DNA.
750 mg per day for 5-10 days or 2-4 gm per day for 2days.
Metallic after taste, nausea, vomiting, diarrhoea. Rarely sensory neuropathy, ataxia, vertigo,seizuresencephalopathy
Inhibits protein synthesis
2 gm per day for days or 1-1.5 mg / kg / day for 5 days.
Rapid amoebicidal activity.
Cardio toxicity, diarrhoea, nausea, vomiting, muscle weakness.
Amino glycoside-inhibit protein synthesis.
30mg/kg/day in 3 divided dose for 5 to 10 days.
Poorly absorbed amino glycoside with excellent safety profile.
Nausea, vomiting, cramps, diarrhoea.
500 mg tid for 10 days
Poorly absorbed antibiotic with excellent safety profile.
650 mg tid for 20 days
Poorly absorbed agent
Headache, nausea, vomiting, optic nerve damage and peripheral neuropathy