This document provides information on a presentation about pharmaceutical approaches to colon targeted drug delivery systems for treating diseases like Crohn's disease. It discusses the anatomy and physiology of the colon, diseases associated with the colon, drug absorption in the colon, and various approaches for colon targeted drug delivery including pH sensitive polymers, time controlled release systems, microbiologically triggered systems, and new approaches like pressure controlled, pulsatile, and multi particulate systems. The presentation aims to highlight the advantages and limitations of different colon targeted drug delivery approaches.

1. A
PRESENTATION
ON
PHARMACEUTICAL APPROACHES TO COLON
TARGETED DRUG DELIVERY SYSTEM
& Crohn’s Diseases
• Presented by :Dishant Shah
• 15MPH104
• Email ID:- 15mph104@nirmauni.ac.in
• Presented to: Dr. Tejal Mehta
• DEPT. OF PHARMACEUTICS

2. INTRODUCTION
Colon drug delivery has gained
increased importance not only for the
treatment of local diseases
associated with colon but also for its
potential for the delivery of proteins
and therapeutic peptides

3. ANATOMY OF COLON

4. ANATOMY AND PHYSIOLOGY
OF COLON
Create suitable environment
microorganisms.
for colonic
Storage reservoir of faceal matter .
Expulsion of the contents of the colon.
Absorption of potassium & Water from the lumen
MAJOR
FUNCTIONS OF
COLON

5. DRUG ABSORPTION FROM COLON
Colon contents—More viscous with progressive absorption
of water & delays the diffusion of drug
from the lumen to mucosa
LIPOPHILIC DRUG
HYDROPHILIC
DRUG

6. DISEASES ASSOCIATED WITH COLON
 INFLAMMATORY BOWEL DISEASES
i)CROHN’ S DISEASE
ii)ULCERATIVE COLITIS




COLORECTAL CANCERS
AMOEBIASIS
DIVERTICULOSIS
DIARRHOEA

8. • Crohn’s disease is an idiopathic
inflammatory bowel disease characterized
by transmural non caseating granulomatous
inflammation.

9. Complications
Intestinal
complications
Stricture
Fistula
Perforation
Abscess
Neoplasm
Systemic
complications
Arthritis
Ankylosing spondylitis
Sclerosing episcleritis
Uveitis
Sclerosing cholangitis
Oxalate stones
Erythema nodosum
Pyoderma
gangrenosum
Postoperative
complications
Anastomotic
recurrence
Anastomotic
fibrostenosis
Adhesional obstruction

11. ADVANTAGES
 Increases the absorption of poorly
absorbable drugs due to high retention
time of colon
 Minimizes first pass metabolism
 Decreases the side effects in associated
with the treatment of colon diseases
 Provides suitable environment for the
absorption peptides & proteins that are
sensitive to gastric fluid

12. LIMITATIONS
 Multiple manufacturing steps.
 The resident microflora could also affect colonic
performance via metabolic degradation of the drug.
 Bioavailability of drug may be low due to potentially
binding of drug in a nonspecific way to dietary
residues, intestinal secretions, mucus or faecal matter.
 Viscosity of luminal contents is high which hinder he
dissolution & drug release from the formulation

13. PHYSIOLOGICAL
FACTORS
PHARMACEUTICAL
FACTORS
Transit time
Drug candidates
pH of colon
Drug carriersColonic Microflora
and enzymes

14. PHYSIOLOGICAL FACTORS
TRANSIT TIME
Transit time of dosage
form is highly variable &
depends on
Subject Fed / fasted.
Food increases transit
residence
Properties of dosage
form (Size & Density).
Fasted state 10min
-2hrs
Fed state >2 hrs
Small
intestinal
transit
3-4 hrs
Colonic
transit
20-35 hrs

15. PH OF COLON
PH Varies through out the GIT which leads to earlier
disintegration and dissolution of drug
Stomach
Fasted state
Fed state
1.5-2
2 – 6
Small intestine 6.6 – 7.5
Ascending colon
Transverse colon
Descending colon
6.4
6.6
7.0

16. PHARMACEUTICAL FACTORS
  Selection of carrier
depends on nature of
drug
Should be poorly
absorbed from
stomach & small
intestine  Physiochemical
factors like chemical
nature, stability should
be considered while
selecting the carrier
 PHStable at alkaline
of GIT
DRUG CARRIERDRUG CANDIDATE

17. APPROACHES FOR COLON TARGETEDDRUG
DELIVERY SYSTEM
PRIMARY APPROACHES
NEW APPROACHES

18. PRIMARY APPROACHES
CTDDS
FOR
PRIMARY
APPROACHES
PH sensitive polymer
Coated DDS
PRODRUGAPPROACH
Delayed release DDS
POLYSACCHARIDE BASED
SYSTEM
Microbiologically
triggered DDS

19. PH1. SENSITIVE POLYMER COATED
SYSTEM
This system is based on solubility of
PHdifferent polymers at different range, as
PHthe varies at different parts of GIT
PHPolymers are insoluble at lower & get
colonPHsolubilised as the increases i.e.,
So formulation can be protected in
stomach &
intestine
pH sensitive
polymer +
drug core
to some extent in Small
Release of drug in
Colon
Colonic pH

22. Drug Trade Name Coating Polymer / Formulation
Budesonide Entrocort®
Budenofalk®
Targit®
Eudragit® L 100-55, ethyl cellulose
Eudragit® S (Dissolution pH-7)
Coated Starch Capsule
Mesalazine Claversal®
Asacolitin®
Salofalk®
Pentasa®
Mesazal®
Calitofalk®
Asacol ®
Eudragit® L100 (Dissolution pH-6)
Eudragit® S (Dissolution pH-7)
Eudragit® S (Dissolution pH-6)
Ethyl cellulose coated pellets
Eudragit® L100 (Dissolution pH-6)
Eudragit® L100 (Dissolution pH-6)
Eudragit® S (Dissolution pH-7)
Mesalazine Azulfidine®
Colo-Pleon®
Cellulose acetate phthalate (Dissolution
pH-
6.2-6.5)
Eudragit ® L100-55 (Dissolution pH-5.5)

23. 2.TIME CONTROLLED RELEASE
DRUG DELIVERY SYSTEMS
 This approach is based on the principle of
delaying the release of the drug until it enters into
the colon.
 The strategy in designing timed-released systems
and to undergo a lag time of predetermined span
of time, after which release of drug take place.
is to resist the acidic environment of the stomach
 The lag time in this case is the time required to
transit from the mouth to colon

24. Lag phase of
~ 5 h is
observed.

25. 3.MICROBIOLOGICALLY TRIGGERED
DRUG DELIVERY SYSTEMS
 The microflora of the colon, mainly consists of
bifidobacteria, eubacteria, clostridia, enterococci
etc.
anaerobic bacteria, e.g. bacteroides,
 This microflora fulfills its energy needs by
fermenting various types of substrates that have
been left undigested in the small intestine, e.g. di-
and tri-saccharides, polysaccharides etc.
 For this fermentation, the microflora produces a
galactosidase etc which are capable of degrading
the polymers in the formulation targetted for colon
vast number of enzymes like glucouronidase,

26. Bacterial count in the colon is much higher around
𝟏𝟎 𝟏𝟏
-𝟏𝟎 𝟏𝟐
CFU/ml.
400 species
Fundamentally anaerobic in nature.
Predominant species: Bacteroides, Bifidobacterium
and Eubacterium.
Major metabolic processes occurring in the colon are
hydrolysis and reduction.

27. Colonic Microflora
Human intestinal microflora distribution in number
(Log 10- scale) per gram faeces.

28. i) PRODRUG APPROACH
Prodrug is inactive form of parent drug that
undergoes enzymatic transformation to release the
active drug
Prodrugs are prepared by linking the active drug
with hydrophobic moieties like amino acids,
glucose
Most widely used prodrug approaches are
Azo prodrugs
Dextran prodrugs
Cyclodextrins prodrugs
Glycoside prodrugs

29. PRODRUG APPROACH

30. CPS,JNIST,13031S0304
ii) POLYSACCHARIDE BASED DRUG
DELIVERY SYSTEM
 Natural
mixed
polysaccharides are either modified or
with water insoluble polymers like
guargum,chitosan,alginates
 This polysaccharides are broken by colonic
microflora to simple polysaccharides

31. NEW APPROACHES FOR
COLON DRUG DELIVERY
TARGETED
SYSTEMS
PRESSURE CONTROLLED DDS
CODES
OSMOTIC CONTROLLED DDS PULSINCAP
PULSATILE DDS
PORT SYSTEM
AZO HYDROGELS
MULTIPARTICULATE SYSTEM BASED DDS

32. 1. PRESSURE CONTROLLED DRUG
DELIVERY SYSTEM
 Relies on the relatively strong peristaltic waves
that occur in the colon which leads to an increased
luminal pressure, in response to raised pressure of
the colon, the dosage form get ruptured and
release the drug at desired site.
 The intestinal pressure developed varies with
circadian rhythms, state of the body

33. 1. PRESSURE CONTROLLED DRUG
DELIVERY SYSTEM
PCDDS consists of drug in a capsule coated with
water insoluble polymer like Ethyl cellulose
Drug is introduced in to the capsule along with
suppository base. After administration suppository
base dissolves & water is absorbed in to the
capsule resulting in increased pressure in the
capsule
System can be developed in such a way that
withstands the pressure in intestine and ruptures
in response to raised pressure in colon due to
peristaltic movement

34. 2.CODESTM
POLYSACCHARIDE COATING
 This System consists of a core tablet
coated with 3 layers of polymer coating
 Outer coating : Enteric coating which
protects the tablet in stomach
 Middle coating : Acid soluble coating which
protects the tablet in intestine
 Inner coating : polysaccharide layer, which
gets degraded by microbes upon reaching
the colon.
ACID SOLUBLE COATING
ENTERIC COATING

35. CPS,JNIST,13031S0304
CODESTM

36. 3.OSMOTICALLY CONTROLLED
DRUG DELIVERY SYSTEM
The OROS-CT system can be single osmotic
unit or may incorporate as many as 5-6 push-
pull units, each 4mm in diameter, encapsulated
with in 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.

37. CPS,JNIST,13031S0304
OSMOTICALLY CONTROLLED
DRUG DELIVERY SYSTEM

38. OSMOTICALLY CONTROLLED DRUG DELIVERY
SYSTEM
 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 enter the small intestine, the coating
water enters the unit, causing the osmotic unit to
swell and forces drug gel out of orifice at a
controlled rate.
dissolve in this higher pH environment (pH >7),

39. i) PULSNICAP SYSTEM
4.PULSATILE COLON TARGETED DRUG DELIVERY
SYSTEMS
It consists of enteric coated capsule containing
water soluble cap and water insoluble body.
The body is loaded with Hydrogel plug and drug
layer
Enteric coat dissolves in small intestine and the
water soluble cap also dissolves.
The Hydrogel plug absorbs water and swell and
release drug at a predetermined lag time of 4 hours
i) PULSINCAP SYSTEM

40. CPS,JNIST,13031S0304
PULSINCAP SYSTEM

41. ii) PORT SYSTEM
 In this system capsule body with
osmotically active agent and drug
formulation is enclosed in semi permeable
membrane
When capsule comes in contact with the
dissolution media, semi permeable
membrane permits the fluid flow in to the
capsule resulting in development of
pressure in the capsule which leads to drug
release


42. PORT SYSTEM

43. CPS,JNIST,13031S0304
PORT SYSTEM

44. 5.MULTI PARTICULATE SYSTEM BASED DRUG
DELIVERY
Multi particulate system includes
pellets,Microparticles,granules,nano
particles
Multi particular system is more
preferred over single dosage forms as
this system enables the drug to reach
the colon quickly and retain for a
longer period of time

45. MULTI PARTICULATE SYSTEM
BASED DRUG DELIVERY

46.  Philips’ Intelligent pill
 Enterion Capsule
 InteliSite® capsule

47. Philip’s Intelligent pill
Is device of ‘Philips research’ available in market from 2008
 The ‘iPill’ is a capsule and it has
been designed to be swallowed
and to pass through the digestive
track naturally. It can be
electronically programmed to
control the delivery of medicine
according to a pre-defined drug
release profile.
The iPill determines its location in the intestinal tract by
measuring the local acidity (pH difference) of its
environment.

48.  The iPill releases medicine from its drug reservoir via a
microprocessor controlled pump, allowing accurate
programmable drug delivery.
 The capsule is designed to measure local temperature, and
report measurements wirelessly to an external receiver
unit.

49. It can be used in treatment of Crohn’s disease,
Ulcerative colitis and Colon cancer.

50. Enterion Capsule
The Enterion capsule has been developed by Phaeton
Research, Nottingham, UK, for targeted delivery of a
wide range of different drug formulations into any region
of the colon.
The capsule can be loaded with either a liquid
formulation (eg. solution, suspension) or a particulate
formulation (eg. powder, pellets, Minitab lets, etc.)
The floor of the drug reservoir is the piston face, which is
held back against a compressed spring by a high-tensile
strength polymer filament. A radioactive marker is placed
inside a separate sealed tracer port to allow real-time
visualization of the capsule location using the imaging
technique of gamma scintigraphy.

52. When the capsule reaches the target location in the
gastrointestinal tract, the contents are actively ejected by
the external application of an oscillating magnetic field.
This magnetic field induce power in a tuned coil antenna,
embedded in capsule wall. This power is fed to a tiny
heater resistor located in capsule.
This heater resistor increases temperature & releases the
spring & drives the piston.
The resulting increase in pressure within the drug
reservoir forces off the O-ring sealed cap and ejects the
drug or drug formulation into the surrounding GI fluids.

54. InteliSite® capsule
The InteliSite®
capsule is an
ingestible, radio-
controlled device
capable of
delivering either
liquid or powder
drug formulations,
on demand, to a
specific region of
the gastrointestinal
tract.

55. The InteliSite® capsule is loaded with a drug solution or
powder formulation in a specially designed reservoir.
When the capsule reaches the desired location in the
gastrointestinal tract it is externally activated by remote
control.
Activation is accomplished by exposing the capsule to a
radio frequency magnetic field that induces a small
amount of heat in the capsule's activation assembly. This
causes two shape-memory alloy wires to straighten,
rotating an inner sleeve of the capsule in relation to an
outer sleeve.

56. The rotation process aligns a series of slots in the sleeve
surfaces permitting the contents to be released into the
specific area of the GI tract. After activation, the
InteliSite® capsule passes harmlessly through the body.

57. EVALUATION PARAMETERS
EVALUATION PARAMETERS
INVITRO EVALUATION
INVIVO EVALUATION
CLINICAL EVALUATION

58. INVITRO EVALUATION
 Invitro evaluation includes
i)in vitro dissolution
ii)in vitro enzymatic
study
test
 Dissolution is done using conventional
basket method in different buffers to
characterize the behavior of formulations at
PHdifferent levels
In vitro dissolution study

59. INVITRO EVALUATION
 Includes two tests
I) Drug system is incubated in fermenter
containing suitable media for bacteria, amount
drug released at time intervals is determined
ii)Drug release study is performed in different
buffer medium containing enzymes or cecal
contents
of
 The amount of drug released in a particular time
directly proportional to the rate of degradation of
polymer
is
INVITRO ENZYMATIC TEST

60. IN-VIVO EVALUATION AND
CLINICAL EVALUATION
 It is done in rats, dogs as they resemble
anatomical &physiological conditions
microflora of human GIT
and
 Absortion of drugs from colon can be
monitored by colonoscopy and intubations
CLINICAL EVALUATION
INVIVO EVALUATION

61. REFERENCES
.
.
.
Pulsincap System For Colonic Drug Delivery by
HowardN.E.Stevens
The Enterion Capsule by David V. Prior, Alyson L.
Connor, and Ian R. Wilding*
InteliSite Capsule - Data courtesy of Scintipharma, Inc. -
Lexxington, Kentucky U.S.A.
 Vincent H.L. Lee and Suman k. Mukherjee ;
Encyclopedia of pharmaceutical Technology.
Edi 2007
 Van den Mooter G. V., Kinget R, (1995) Oral
colon-specific drug delivery: a review
DrugDeliv, 2: 81-93.
 Sarasija S, Hota A. (2002) Colon-specific drug
delivery systems. Ind J Pharm Sci. 62(1):1-8.

62. CPS,JNIST,13031S0304