"A REVIEW ON COLONIC DRUG DELIVERY"

A
DISSERTATION OF
Submitted in Partial Fulfilment for the requirement for the Award of
Degree of Bachelor of Pharmacy
Submitted To

RAJIV GANDHI PROUDYOGIKI VISHWAVIDYALAYA BHOPAL (M.P)

Submitted By
Dilip Uikey
0146PY161022
B.Pharma-VII Sem.
Under Supervision of

Mr. Dharmendra Singh Rajput

(Associate Professor)

PATEL COLLEGE OF PHARMACY

BHOPAL (M.P)
 PATEL COLLEGE OF PHARMACY
BHOPAL (M.P.)

CERTIFICATE
This is to certify that DILIP UIKEY Enrollment No. 0146PY161022 has carried out
the work presented in the project entitled “A REVIEW ON COLONIC DRUG
DELIVERY “ for the award of “Bachelor of Pharmacy” from “Rajiv Gandhi
Proudyogiki Vishwavidyalaya, Bhopal(M.P)” under my supervision The project
embodies result of original work, and studies are carried out by the student himself
and the contents of the project do not from the basis of the award of any other degree
to the candidate or to anybody else from his or any other university or institutions.

Approved By:-

Dr. Shailesh Jain Mr. D.S. Rajput External

…………………. ……………….... ………...
Principal Guide
(PCP Bhopal) (PCP Bhopal) Date…./…./….

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 ACKNOWLEDGEMENT

I take this opportunity to thank Mr. Dharmendra Singh Rajput work under
their valuable guidance, closely supervising this work over the past few months
and offering many innovative ideas and helpful suggestions, valuable advice and
support. In spite of their busy schedule they have really been an inspirations and
driving force for me. They have constantly enriched my raw ideas with their
experience and knowledge.

DATE: DILIP UIKEY

0146PY161022

Patel College Of Pharmacy Bhopal

 PATEL COLLEGE OF PHARMACY
BHOPAL (M.P.)

FORWARDING LATTER
DILIP UIKEY student of B. Pharma VII semester at PATEL COLLEGE OF
PHARMACY Bhopal has completed his project work on topic entitled “COLONIC
DRUG DELIVERY” under the supervision of Mr. Dharmendra Singh Rajput,
Assistant Professor Patel College Of Pharmacy, Bhopal for the fulfilment of degree of
Bachelor of Pharmacy.

This dissertation is forworded to examiner for evaluations.

Date:

Place: Principal

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INTRODUCTION

Traditionally solid oral dosage firms have been designed to release their drug load in
upper regions of G.I.T. Where conditions are generally more suited to drug dissolution
and absorption. Recently greater emphasis has been placed on controlling the rate and
site of drug release from oral formulations for the purpose of patient compliance and
treatment efficiency.

The colonic region of G.I.T is one that would benefit from the development and such
modified release technologies. Although considered by many to be an innocence organ
that may simple functions in the form of water and electro light absorption and the
formation storage and explosion of fecal material, the colon is valuable to a No of
disorders including alternative qualities corn's disease irritable bower syndrome and
carcinomas. Targeted drug delivery to the colon would therefore ensure direct treatment
at the disease site lower closing and favour systemic side effects.

In addition to local therapy, the color can also be utilized as a portal for entry of drug
into the systemic circulation. eg:- molecules that are degraded parry absorbed in upper
get, such as peptides and proteins, may be better absorbed from more being environment
of colon . In addition systemic absorption from colon can also be used as a means of
achieving chemotherapy for diseases that are sensitive to circadian rhythms such as
asthma angina, orthotics.

Successful colonic drug delivery careful consideration of a large number of factors,

including the properties of drug, the type of delivery system and in interaction with the
healthy or diseased gut for instance, regardless of whether a local or systemic effect is
required, the administrate drug must first dissolve in lonely fluid of colon. Overseas,
there is less free fluid in colon than is small intestine and hence, dissolution could be
drug may need to be delivered in a pre-established form, or delivery should be directed
to proximal colon, as a fluid gradient exists in colon with more free water present in
proximal colon than is distal colon.

Aside from drug solubility, the stability of drug in colonic environment is a further
factor that warrants attention. The drug could bind in a non specific manner to directory
residues, intestinal secretions, or general faucal matter, thereby reducing the connection
of free drug. Moreover, the resident microflora caved also effect colonic performance
via degradation of drug.

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 In terms of systematic therapy via the colon, the small internal surface area and
relative 'tightness' of tight junction is colon could restrict drug transport across mucosa
a enzymes that are capable of metabolizing endogenous and exogenous subtracts such
as carbohydrates , proteins, that escape digestion in upper G.I tract ,

.Therefore materials that are recalcitrant to the conditions of stomach and small
intensive, yet suspicious to degradation by bacterial enzymes within colon, can be
utilized as carriers for drug delivery to colon.

Eg:- This principle has been exploited commercially to deliver 5 anniosalicylic acid
to the colon by way of a prodrug career. The prodrug sulphasalazine consists of two
separate moieties, sulphaphyridine and 5-aminosalcylic acid, linked by as azo-bond.
The prodrug posses through the upper gut intract, but once in colon the azo-bond is
cleave by the host bacteria, liberating the carrier molecule sulphaphyridine and
pharmacologically active agent 5- aminosalicyclic acid and its systematic circulation.
To a certain earnest, the longer residence time in colon (up to 5 says) may compensate
for these limitations. There is also evidence to suggest that the activity of the cyclo
chrome p 450 3A class of drug metabolizing enzymes is lower is mucosa of colon than
small intensive. Therefore colonic delivery may lead to elevated plasma levels and
improved oral bioavailability for drugs that are substrates for this enzyme class.In
relation to delivery modified release formulations are usually based on either a single
unit tablets and bicapsular) or multi unit (Pellets & granules) plat form design.

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TARGETTING MECHANISM OF DRUG ACTING ON COLON

1. Pre-dependent delivery
2. Time-dependent delivery
3. Pressure-dependent delivery
4. Bacteria dependent delivery

Successful colonic drug delivery requires careful considerations of a number of factors,

including the properties of drug, the type of delivery system and its interaction with the
healthy or diseased gut.

1. PH - DEPENDENT DELIVERY

Pre-sensitive enteric coatings have been used routing to deliver drugs to small
intensive. These polymer coatings are insensitive to the acidic conditions of stomach
yet dissolve at the higher PH environment of small intestine. This Ph differential
principle has also been attempted for colonic delivery purposes although polymers used
for solenoid targeting and to have a threshold PH for dissolution that is HIGHER than
those used in conventional enteric coating applications. Most commonly co-polymers
of methacrylic acid and methyl metha crylate that dissolve at PH 5 PH 7 have been
investigated./ This approach is based on assumption that G.I PH increases progressively
from the small intestine to colon. In fact, the in distal small intestine is usually around
7.5, while the H in proximal colon is closer to 6 These delivery systems therefore have
a tendency to release their drug load prior to reaching colon.

To overcome the problem of premature drug release a copolymer of methacrylic,

acid, methyl methacrylate and ethy threshold OH, has been developed recently.

The inter subject variability in G>I PMand possibly certain other intersect various
such as electrolite concentration.and transit time will therefore impact on in vivo
behaviour of PH responsive systems, ranging from early drug release is small intensive
to are release at all with the formulation passing throughout gut intact. The latter
situation will also arise when PH of colon, and possibility the small intensive is
considerably lower than normal as the case in patients with creative qualities.. In spite
of their limitations, PH sensitive delivery systems are commercially available for
mesalazine in and budesonide for treatment of ulcerative colitis & crohn's disease,
respectively.

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2. TIME DEPENDENT DELIVERY

It has also been proposed as a means of targeting the colon. Time dependence systems
release their drug load after a pre programmed time delay. To attain colonic release, the
log, time should equateto time taken for system to react the colon. This time is difficult
to predict in advance,although a log time of five hours is usually considerated sufficient,
given that small intential transit time is reported to be relatively consitant at three to
four hours. One of the earliest system to utilise this principle was the pulsincap device.
System consisit of an importable capsule fined with drug and stoppered at one end with
a hydroges plug, on contact with gastrointential fluids, the plug hydratres and swells
and after a set log time, ejects from the capsule body, thereby allowing drug release to
occur. The log time is controlled by the size and composition of play. The influ

BACTERIA DEPENDENT DELIVERY

The resident g.i.bacteria provide a further means of effecting drug release in colon,
These bacteria predoninatly colonise the distas region of g.i tract where baterial count
in the colon is 10' per gramme as compared with 10'per gramme in uper small inestine
moreover, 400 different species are present colonic bacteria are pre dominantly in nature
and produce ence of gastric copying on performance of pulsincap was reduced by a
application of an outer enteric coat. The outer enteric coat dissolves on entering the
small intenstine to reveal by either swelling, eroding or dissolving over a period of time
equivalant to small intential transit.

Although the use of an over enteric coat overcomes to a certain attent the availability
in G.I emptying, the intrisic problems with such systems is over all inter and intra
subject variability in transit. Transit is slower in evening as compared with morning.

3. PRESSURE DEPENDENT DELIVERY

G.I pressure has also been utilised drug release in destal gut.This pressure which is
generated via muscular contraction of gut wall for gtinding and proposition of intestial
contents, varioes in intesity and duration throught the g.itract, with the colon considered
to have a higher internal pressure due to process that ocur during stool formation. The
system have therefore been developed to resisst the pressure of upper g.i tract but in
rupture response to the raised pressure of colon.capsule shells fabricated from water
insolube polymer entry cellulose have been used for this purpose. The system can be
modified to withstand and rupture at different pressors by changing the size of capsule
and thicknessof capsule shell wall.

enzynes that are capable of metabolishing endogenous and exogeneous substracts such
as carbohydrates ,protines,that escape digestion in upper g.i tract ,.Therefore materials

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that are recalcitrant to the conditions of stonach and small intensive, yet suspecious to
degradation by bacterial enzynes within colon, can be ulilised as carriers for drug
delivery to colon.

Eg:- This principle has been expoited commercially to deliver 5 anniosalicylic acid
to the colon by way of a prodrug career. The prodrug sulphasalazinc consists of two
separate moities, sui phaphyridine and 5-aminosalcylic acid, linked by as azo-bond. The
prodrug posses through the upper gut intract,but once in colon the azo-bond is cleaveal
by the host bacteria, liberting the carrier molecule sulphaphyridin and
pharmacologicary active agent 5- aminosalicyclic acid.

PHARMACEUTICAL APPROACH TO COLON TARGETED

DRUG DELIVERY

COATING WITH BIODEGRADABLE POLYMERS

The bio environment inside the human G.I.T is characterized by presence of complex
microflora especially the colon that is rich in micro organizing that are involved in the
process of reduction of dietary component or other materials. Drugs that are coated with
polymers, which are showing degradability due to influence of colonic micro
organisms, can be exploited in designing drugs for colon targeting. These bacterial
degradable polymers especially also polymers have been explored in order to release as
orally administrated drug in colon. Actually upon passage of dosage from through G.I.T
it remains intact in stomach and small intestine where very little microbially degrades
activity is present that is quiet insufficient for cleavage of polymer coating, Release of
the drugs from azo polymer coated formulation is supposed to take place after
reductionism thus degradation of azo bonds by azo reductase enzymes released by azo
batters in colonic microflora.

Mesalazine is the active component of sulfasalazine exerting a predominant local

topical action independent of blood levels. Its effectiveness depends on the site of

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ulceration in relation to the drug's dissolution profile. This is very important when
choosing aminosalicylate preparations, as illustrated in Figure 11.4.

The optimal dose of sulfasalazine to achieve and maintain remission is usually in the
range of 2-4g pe day in four divided doses. Acute attacks require 4-8g per day in divided
doses until remission occurs, but at these doses associated side-effects begin to appear.

Of patients taking sulfasalazine, 30% experience adverse effects that are either dose-
related, dependent on acetylator phenotype or idiosyncreatic non-dose, related
reactions. The first group includes nausea, vomiting, headache, malaise, haemolytic
anaemia, reticulocytosis, and methamemoglobulinaemia. The second includes skin
rash, hepatic and pulmonary dysfunction, aplastic anaemia and reversible azoospermia.
Adverse effects usually occur during the first 2 weeks of therapy, the majority being
related to serum sulfapyridine levels.

Many of the adverse effects listed above can be avoided by using one of the
aminosalicylate formulations now available.

Formulation. As mesalazine is unstable in acid medium and rapidly absorbed from

the gastrointestinal tract, the new preparations have been developed using three
different approaches.

• A mesalazine tablet coated with a pH-dependent acrylic resin

• Ethylcellulose-coated mesalazine granules diazotization of mesalazine
to itself or to an inert carrier.

Asacol contains 400 mg of mesalazine coated with an acrylic resin, Eudragit-S, that
dissolves at pH 7 and releases mesalazine in the terminal ileum and the colon.
Salofakd tablets are similar fo;umulation containing 250 mg mesalizine with sodium
carbonate-glycine and a cellulose ether, coated with Eudragit-L which dissolves at pH
6 and above, releasing mesalaxine in the jejunum and ileum.

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Table 11.4 comprasion of available oral aminosalicylate premations for patients with
inflammatory bowel disease
Generic
(proprietary) Formulation Release profile Site of release
name

Sulfasalazine Compressed tablet. Plain and Azo-linked, Terminal ileum

(Salazpyrin) film coated independent at pH and colon

Mesalazine Compressed tablet, acrylic Acrylic coating Terminal ileum

(Asacol) coating dissolving at pH 7 and colon

Mesalazine
Compressed tablet and/or Acrylic coating Mid-jejunum
(Salofalk and
capsule acrylic coating dissolving at pH 6 ileum and colon
generic forms)

Microgranules coated with Stomach,

Disintegration not
Mesalazine ethycellulose and compressed duodenum,
dependent on pH.
(Pentasa) into tablets. Granules also jejunum, ileum
Slow dissolution rate
available and colon

Azo-linked
Olsalazine Hard gelatin capsules and Terminal ileum
disintegration
(Dipentum) tablets, uncoated and colon
independent of pH

Azo-linked
Balsalazide Terminal ileum
Hard gelatin caplules disintegration
(Colazide) and colon
independent of pH

Azo linked
Terminal ileum
Polyasa Compressed tablet disintegration in
and colon
dependent of ph

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COVALENT LINKAGE OF THE DRUG WITH A CARRIER

It involves the formation of a covalent linkage between drug and carrier in such a
manner that upon oral administration the moiety remains intact in the stomach and small
intestine.

This approach chiefly involves the formation of prodrug, which is a

pharmacologically inactive derivative of a parent drug molecule that requires
spontaneous or enzymatic transformation in the biological environment to release the
active drug. Formation of prodrugs has improved delivery properties over the parent
drug molecule. The problem of stability of certain drugs from the adverse environment
of the upper GIT can be eliminated by prodrug formation, which is converted into parent
drug molecule once it reaches into the colon. Site specific drug delivery through site
specific prodrug activation may be accomplished by the utilization of some specific
property at the target site, such as altered pH or high activity of certain enzymes relative
to the non-target tissues for the prodrug-drug conversion.

AZO BOND CONJUGATES

The intestinal microflora is characterized by a complex and relatively stable community

of microorganism, many with physiological functions, which play vital roles in health
and disease. In addition to protection of the patient against colonization of the intestinal
tract by potentially pathogenic bacteria, the indigenous microflora are responsible for a
wide variety of metabolic processes, including the reduction of nitro and azo groups in
environmental and therapeutic compounds.

Sulphasalazine was introduced for the treatment of rheumatoid arthritis and anti-
inflammatory disease. Chemically it is salicylazosulphapyridine (SASP), where
sulfapyridine is linked to a salicylate radical by an azo bond. When taken orally, only a
small proportion of the ingested dose is absorbed from the small intestine and the bulk
of the sulphasalazine reaches the colon intact. There it is split at the azo bond by the
colonic bacteria with the liberation of sulphapyridine (SP) and 5 ASA. However
sulphapyridine is seems to be responsible for most of the side effects of sulphasalazine
and hence various new approaches for the treatment of IBD have emerged.

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GLYCOSIDE CONJUGATES

Steroid glycosides and the unique glycosidase activity of the colonic microflora
frorm the basis of a new colon targeted drug delivery system. Drug glycosides are
hydrophilic and thus, poorly absorbed from the small intestine. Once such a glycoside
reaches the colon it can be cleaved by bacterial glycosidases, releasing the free drug to
be absorbed by the colonic mucosa.

The major glycosidases identified in human feces are b-D-galactosidase, b-D

glucosidase, a--L-arabinofuranosidase, b-D-xylopyranosidase. These enzymes are
located at the brush border and hence access to the substrate is relatively easy. In the
plant kingdom numerous compounds are found as glycosides. Certain drugs act as
glycon and can be conjugated to different sugar moieties which results in the formation
of glycosides. Due to the bulky and hydrophilic nature of these glycosides, they do not
penetrate the biologicl membrane upon ingestion. Various naturally occurring
glycosides, e.g the sennosides, have been used for laxative action for ages. When taken
orally, intact sennosides are more efficient as laxative than sugar free aglycones. These
sennosides are activated are activated by colonic microflora to generate rhein anthones,
which gives the desired laxative effect. Glycosidase activity of the GIT is derived from
anaerobic microflora in the large bowel or the sloughed or exfoliated cells of the small
intestine.

GLUCURONIDE CONJUGATES

Glucuronide and sulphate conjugation is the major mechanisms for the inactivation
and preparation for clearance of a variety of drugs. Bacteria of the lower GIT, however,
secrete b-glucuronidase and can deglucuronidate a variety of drugs in the intestine.
Since the deglucuronidation process results in the release of active drug and enables its
reabsorption, glucuronide prodrugs would be expected to be superior for colon targeted
drug delivery.

Morphine-dependent rats were used to evaluate the effects of the narcotic antagonists,
naloxone and nalmefene, and their glucuronide conjugates on the gastrointestinal tract
and various parameters of brain-mediated withdrawal. When administered
subcutaneously nalmefene hydrochloride caused a dose-dependent tail skin temperature
increase, whereas nalmefene glucuronide was ineffective Malmefene precipitated
brain-mediated morphine with drawal at doses as low as 10mg/kg, whereas nalmefene
glucuronide was ineffective at doses as high as 1mg/kg. After per oral administration
of the drugs, nalozone hydrochloride and nalmefene hydrochloride caused diarrhea,
withdrawal behavior and tail skin temperature responses by 15 minutes. In contrast,

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after per oral administration of the glucuronide conjugate of either narcotic antagonist,
diarrhea was delayed for 75 to 203 minutes. This latency probably reflects the required
transit time to the lower gastrointestinal tract. About 0.2 to 0.5% of the dose of the
narcotic antagonist administered orally as the glucuronide was absorbed systemically.
These results indicate that per oral administration of the glucuronide conjugates of nalox
one and nalmefene results in delivery of the narcotic antagonists to the colon. Haeberlin
et al. prepared a dexamethasone b-D-glucuronide prodrug.

CYCLODEXTRIN CONJUGATES

Cyclodextrins (CyDs) are clyclic oligosaccharides consisted of six to eight glucose

units through a-1,4 glucosidic bonds and have been utilized to improve certain
properties of drugs such as solubility, stability and bioavalability. The interior of these
molecules is relatively lipophilic and the exterior relatively hydrophilic, they tend to
form inclusion complexes with various drug molecules. They are known to be barely
capable of being hydrolyzed and only slightly absorbed in passage through the stomach
and small intestine, however, they are fermented by colonic microflora into small
saccharides and thus absorbed in the large intestine. Because of their bioadaptability
and multi functional characteristics, CyDs are capable of alleviating the undesirable
properties of drug molecules in various routes of administration through the formation
of inclusion complexes. In an oral drug delivery system, the hydrophilic and ionizable
CyDs can serve as potent drug carriers in the immediate release and delayed release
formulations, respectively, while hydrophobic CyDs can retard the release rate of water-
soluble drugs. Since CyDs are able to extend the function of pharmaceutical additives,
the combination of molecular encapsulation with other carrier materials will become
effective and a valuable tool in the improvement of drug formulation. Moreover, the
most desirable attribute for the drug carrier is its ability to deliver a drug to a targeted
site, conjugates of a drug with CyDs can be a versatile means of constructing a new
class of colon targeting prodrugs.

It has been proved through a study in healthy human volunteers that b CyDs are
meagerly digested in small intestine but are completely degraded by the microflora of
the colon. Most bacterial strains that are isolated from human being are capable of
degrading CyDs. It has been proved by their ability to grow on cyclodextrins by utilizing
them as the sole carbon source and by the stimulation of cyclodextrinase activity by as
low as 2-4h of exposure to cyclodextrins. This property of the drug may be exploited
for the formation of colon targeted drug delivery systems. Several CyD conjugates have
been prepared and the enantioselective hydrolysis has described.

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DEXTRAN CONJUGATES

Dextran ester prodrug was prepared and in vitro release revealed that release of
naproxen from prodrug was several folds higher in caecum homogenates than in control
medium or homogenates of the small intestine of pig. The bioavailability of naproxen
after oral administration of a dextran T-70 naproxan ester prodrug in pigs was assessed
by Harboe et al. compared to the administration of an oral solution of an equivalent dose
of naproxen the average absorption fraction for the conjugate amounted to 91%. It was
established that several features of the prodrug indicated that naproxan was released
from the prodrug prior systemic absorption and that drug activation involved the action
of one or more enzyme systems located in the gastrointestinal tract. It was observed in
rabbits, the plasma concentration-time curves for the conjugate were characterized by
an initial lag time of about 2-3h, whereas naproxan was detected in plasma immediately
after per oral administration of the drug compound per sec. The distribution of the
prodrug along the GIT at various times after conjugate administration was assessed
qualitatively by HPLC analysis of conjugated and free naproxan in various segments of
the GIT. From these experiments it was suggested that drug regeneration was effective
in the bowel below the ileum.

AMINO-ACID CONJUGATES

Due to the hydrophilic nature of polar groups like NH2 and COOH, that is present in
the proteins and their basic units, they reduce the membrane permeability of amino acids
and proteins. Various prodrugs have been prepared by the conjuagation of drug
molecules to these polar amino acids. Non-essential amino acids such as tyrosine,
glycine, methionine and glutamic acid were conjugated to SA. The salicyluric acid was
found to be metabolized to SA by the microorganisms of the intestinal flora of rabbit
and dog. The prodrug was absorbed into the systemic circulation from the upper GIT
and hence it was proved unsuitable for delivery of drugs to the colon. By increasing the
hydrophilicity and chain length of the carrier amino acid and decreasing the membrane
permeability of conjugates. This conjugate showed splendid results with minimal
absorption and degradation in the upper GIT and proved suitable for colon targeted
delivery of SA.

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POLYMERIC PRODRUGS

Azo-linked polymeric prodrugs of 5-ASA were prepared and evaluated in simulated

human intestinal microbial ecosystem. Polyamides containing azo grups in the
backbone were prepared and tested in vitro in a reductive buffer or in the bioreactor
medium. It was demonstrated that for the hydrophobic polymer, reduction stops at the
hydrazine stage whereas for a hydrophilic analogue reduction with formation of amine
occurred. The amount of the drug released depend on the nature of the polymer and can
approach that of low molecular weight prodrugs.

USES

I. LOCAL ACTIONS

1. Ulcerative colities.
2. CHRON'S disease.
3. Irritable bower syndrome
4. Metastatic human colon cancer

II. SYSTEMIC ACTIONS

1. Molecules degraded/poorly absorbed from upper G.I.T such as peptides

and proteins are better absorbed from colon,
2. For achieving chemotherapy for diseases that are sensitive to circadian rhythm
such as Asthma, angina, arthritis

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ADVANTAGES:

• Patient compliance and treatment efficacy

• Useful in treatment of ulcerative colitis, chron's disease, irritable bowel
syndrome and carcinomas
• Low dose is required ,so less side effect
• Used for local and systemic action
• Gastric irritation can be avoided

DISADVANTAGES:

• .there is less fluid in colon than in small intestine and hence dissolution is
a problem for water soluble drugs
• binding of drug to dietry residues ,intestinal secretions etc reduce
concentration of free drugs
• some micro flora may degrade the drug
• small luminal surface area and relative tightness of tight Jouncions in
colon, delay the systemic absorption.
• Onset of action is slow.

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 CONCLUSION

The colonic region of gastro intestinal tract become and increasingly

important site for drug delivery and absorption. The targeted drug delivery would
offer considerable therapeutic benefits to patients, in terms of both local and
systemic treatment. Systems that rely on gastrointestinal P4 transit tine or
pressure for release are unlikely to function as reachable and effective colon
specific delivery vehicles colon specialty is more likely to be achieved to systems
that utilize natural materials that are degraded by bacterial enzymes of colonic
origin. Moreover the cost and case of manufacture delivery system are further
considerations that will impact on its likely commercialization and hence,
availability to patient .A bacteria sensitive natural film coating that can be
applied to a range of solid oral dosage forms using conversional processing
technology would therefore appear to be delivery system of choice.

In summary two controlled release mechanism, i.e, time and p4-dependent, could
achieve colonic-specific drug delivery following oral administration. In addition,
both CDDS were relatively in expensive and easy to be manufactured using
conventional pharmaceutical coating technique, and provided the promising
candidates for specifically delivering drug to targeted colon region, in particular
for DS and 5-ASA in this study, respectively.

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 REFERENCES

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Patel College Of Pharmacy Bhopal

 15. Friend, D.R., Glycosides in colonic drug delivery. In: Friend, D.R (Ed).
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