CPS,JNIST,13031S0304
PRESENTED BY
B.KAVITHA
M.PHARMACY 2nd SEM PHARMACEUTICS 13031S0304
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
ANATOMY OF COLON
caecum ascending
COLON
TRANSVERSE
COLON
descending
COLON
COLON
Sigmoid
colon
CPS,JNIST,13031S0304
ANATOMY AND PHYSIOLOGY
OF COLON
Create suitable environment for colonic microorganisms.
Storage reservoir of faceal matter .
Expulsion of the contents of the colon.
Absorption of potassium & Water from the lumen
MAJOR
FUNCTIONS OF COLON
CPS,JNIST,13031S0304
DRUG ABSORPTION FROM COLON
Colon contents—More viscous with progressive absorption of water
& delays the diffusion of drug
from the lumen to mucosa
HYDROPHILIC DRUG
LIPOPHILIC DRUG
CPS,JNIST,13031S0304
DISEASES ASSOCIATED WITH COLON
INFLAMMATORY BOWEL DISEASES
i)CROHN’ S DISEASE
ii)ULCERATIVE COLITIS
COLORECTAL CANCERS
AMOEBIASIS
DIVERTICULOSIS
DIARRHOEA
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
PHYSIOLOGICAL
FACTORS
Transit time
pH of colon
Colonic Microflora and enzymes
PHARMACEUTICAL FACTORS
Drug candidates
Drug carriers
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
PH OF COLON
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
PH Varies through out the GIT which leads to earlier
disintegration and dissolution of drug
CPS,JNIST,13031S0304
PHARMACEUTICAL FACTORS
Should be poorly
absorbed from
stomach & small
intestine
Stable at alkaline PH
of GIT
Selection of carrier
depends on nature of
drug
Physiochemical
factors like chemical
nature, stability should
be considered while
selecting the carrier
DRUG CANDIDATE DRUG CARRIER
CPS,JNIST,13031S0304
APPROACHES FOR COLON TARGETED DRUG
DELIVERY SYSTEM
PRIMARY APPROACHES
NEW APPROACHES
CPS,JNIST,13031S0304
PRIMARY APPROACHES FOR
CTDDS
PRIMARY APPROACHES
PH sensitive polymer Coated DDS
Delayed release DDS
Microbiologically
triggered DDS
PRODRUG APPROACH
POLYSACCHARIDE BASED
SYSTEM
CPS,JNIST,13031S0304
1. PH SENSITIVE POLYMER COATED
SYSTEM
This system is based on solubility of
different polymers at different PH range, as
the PH varies at different parts of GIT
Polymers are insoluble at lower PH & get
solubilised as the PH increases i.e., colon
So formulation can be protected in
stomach & to some extent in Small
intestine
Colonic pH
pH sensitive
polymer +
drug core
Release of drug in
Colon
CPS,JNIST,13031S0304
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 is to resist the acidic environment of the stomach and to undergo a lag time of predetermined span of time, after which release of drug take place.
The lag time in this case is the time required to transit from the mouth to colon
CPS,JNIST,13031S0304
3.MICROBIOLOGICALLY TRIGGERED
DRUG DELIVERY SYSTEMS
The microflora of the colon, mainly consists of anaerobic bacteria, e.g. bacteroides, bifidobacteria, eubacteria, clostridia, enterococci etc.
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 vast number of enzymes like glucouronidase, galactosidase etc which are capable of degrading the polymers in the formulation targetted for colon
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
PRODRUG APPROACH
CPS,JNIST,13031S0304
ii) POLYSACCHARIDE BASED DRUG
DELIVERY SYSTEM
Natural polysaccharides are either modified or
mixed with water insoluble polymers like
guargum,chitosan,alginates
This polysaccharides are broken by colonic
microflora to simple polysaccharides
CPS,JNIST,13031S0304
NEW APPROACHES FOR TARGETED COLON DRUG DELIVERY SYSTEMS
PRESSURE CONTROLLED DDS
OSMOTIC CONTROLLED DDS
PULSATILE DDS
AZO HYDROGELS
MULTIPARTICULATE SYSTEM BASED DDS
PULSINCAP
PORT SYSTEM
CODES
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
2.CODESTM
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.
ENTERIC COATING
ACID SOLUBLE COATING
POLYSACCHARIDE COATING
CPS,JNIST,13031S0304
CODESTM
CPS,JNIST,13031S0304
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.
CPS,JNIST,13031S0304
OSMOTICALLY CONTROLLED
DRUG DELIVERY SYSTEM
CPS,JNIST,13031S0304
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 dissolve in this higher pH environment (pH >7), water enters the unit, causing the osmotic unit to swell and forces drug gel out of orifice at a controlled rate.
CPS,JNIST,13031S0304
4.PULSATILE COLON TARGETED DRUG DELIVERY
SYSTEMS
i) PULSNICAP SYSTEM
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
CPS,JNIST,13031S0304
PULSINCAP SYSTEM
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
PORT SYSTEM
CPS,JNIST,13031S0304
PORT SYSTEM
CPS,JNIST,13031S0304
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
CPS,JNIST,13031S0304
MULTI PARTICULATE SYSTEM
BASED DRUG DELIVERY
CPS,JNIST,13031S0304
EVALUATION PARAMETERS
EVALUATION PARAMETERS
INVITRO EVALUATION
INVIVO EVALUATION
CLINICAL EVALUATION
CPS,JNIST,13031S0304
INVITRO EVALUATION
Invitro evaluation includes
i)in vitro dissolution study
ii)in vitro enzymatic test
Dissolution is done using conventional
basket method in different buffers to
characterize the behavior of formulations at
different PH levels
In vitro dissolution study
CPS,JNIST,13031S0304
INVITRO EVALUATION
Includes two tests
I) Drug system is incubated in fermenter containing suitable media for bacteria, amount of drug released at time intervals is determined
ii)Drug release study is performed in different buffer medium containing enzymes or cecal contents
The amount of drug released in a particular time is directly proportional to the rate of degradation of polymer
INVITRO ENZYMATIC TEST
CPS,JNIST,13031S0304
IN-VIVO EVALUATION AND
CLINICAL EVALUATION
It is done in rats, dogs as they resemble
anatomical &physiological conditions and
microflora of human GIT
Absortion of drugs from colon can be
monitored by colonoscopy and intubations
INVIVO EVALUATION
CLINICAL EVALUATION
CPS,JNIST,13031S0304
REFERENCES
1. Advances in Novel and Controlled Drug Delivery System,
KrishnaiahY.S.R, Satyanarayana S. Colon-specific drug delivery
systems. 1997; 89-110
2. Chaurasia M.K., Jain S.K. Pharmaceutical approaches to colon
targeted drug delivery system. Dr. Hari Singh Gour University, J
Pharm Pharmaceut Sci. 2003; 6(1):33-66.
3. N. K. Jain, Progress in controlled & novel drug delivery system, CBS
publishers & distributers 2010; 405-433.
4. Chien YW. Oral drug delivery and delivery systems. In: Chien YW
(Eds). Novel drug delivery systems. Marcel Dekker Inc. New York
1992, pp.139-196.
5. http://www.thepharmajournal.com/vol1Issue2/Issue_April_2012/5.
CPS,JNIST,13031S0304
Top Related