drug targetting to the colon in stomach

1. COLON
TARGETING
Presented By-
ROHIT
R.K.S.D college of pharmacy, Kaithal
(Hry)
M.Pharma 1st year
(Pharmaceutics)

2. 2
Introduction
Anatomy of colon
Conventional approaches
New approaches
In vitro evaluation
In vivo evaluation
Conclusion
FLOW OF PRESENTATION

3. INTRODUCTION
3
Although oral delivery has become widely accepted route for administration of therapeutic drugs but the
gastrointestinal tract presents several formidable barriers to drug delivery
Oral administration of conventional dosage forms normally dissolve in stomach fluid or intestinal fluid and
absorb from these regions of g.i.t depend on the physiochemical properties of drug
Localized delivery of the drugs in colon is required or in condition where drug needs to be protected from
the hostile environment of upper g.i.t
Colon is attracting interest site for poorly absorbed molecule to have improved bioavailability

4. 4
Treatment ulcerative colitis, crohn’s diseases,
carcinomas and infections
High local concentration and minimizing the side effects
or unnecessary systemic absorption
Colon is rich in lymphoid tissue, uptake of antigen into
mast cells of the colonic mucosa produce rapid local
production of antibodies and this help in efficient vaccine
delivery
Longer retention time (5 days) and appears highly
responsive to agents that enhance absorption
Large intestine is relatively free of peptidase
Traverse the entire alimentary canal in order to reach the
target site.
Presence of food and metabolic enzymes also increases
the physiological complexity
Low colonic luminal fluid volume, higher viscosity, and a
neutral pH rate-limiting factor for colonic absorption
Non-specific interactions of the drug with the colonic
content e.g., dietary residues, intestinal secretions,
mucus, or fecal matter can have a negative influence on
the stability of the drug

5. 5Target sites Disease conditions Drug and active agents
Topical action
Inflammatory Bowel Diseases, Irritable bowel disease and
Crohn’s disease, Chronic pancreatitis
Hydrocortisone, Budenoside,
Prednisolone, Sulfaselazine,
Olsalazine, Mesalazine,
Balsalazide.
Local action Pancreatactomy and cystic fibrosis, Colorectal cancer
Digestive enzyme supplements
5-Flourouracil.
Systemic
action
To prevent gastric irritation
To prevent first pass metabolism of orally ingested drugs
Oral delivery of peptides
Oral delivery of vaccines
NSAIDS, Steroids, Insulin,
Typhoid

6. 6
Criteria Pharmacological class Non-peptide drugs Peptide drugs
Drugs used for local effects in
colon against GIT diseases
Anti-inflammatory drugs
Oxyprenolol, Metoprolol,
Nifedipine
Amylin,Antisense
oligonucleotide
Drugs poorly absorbed from
upper GIT
Antihypertensive and
antianginal drugs
Ibuprofen, Isosorbides,
Theophylline
Cyclosporine,
Desmopressin
Drugs for colon cancer Antineoplastic drugs Pseudoephedrine Epoetin, Glucagon
Drugs that degrade in
stomach and small intestine
Peptides and proteins
Bromophenaramine,
5-Flourouracil,
Doxorubicin
Gonadoreline, Insulin,
Interferons
Drugs that undergo extensive
first pass metabolism
Nitroglycerin and
corticosteroids
Bleomycin, Nicotine
Protirelin,sermorelin,
Saloatonin
Drugs for targeting
Antiarthritic and
antiasthamatic drugs
Prednisolone,
hydrocortisone,
5-Amino-salicylic acid
Somatropin,Urotoilitin

7. 7Inflammatory bowel disease (IBD) is
the umbrella term for a group of
chronic relapsing gastrointestinal (GI)
diseases
Ulcerative colitis is a disease that
causes inflammation and sores (ulcers)
in the lining of the large intestine
Inflammation is confined to the colon,
extends proximally from the rectum
and is continuous
Currently 2 million people in major
terrotries suffer from ulcerative colitis

8. 8
Crohn's inflammation can affect any region of the GI tract, with the terminal
ileum and the colon commonly affected
The inflammation is generally discontinuous in manner
Exact cause of disease is undefined, certain factors have been suggested
to play a role, such as genetics, microbiome, environmental stress and
immune dysfunction
Colon cancer is the second leading cause of cancer-related deaths
worldwide and accounts for 677,000 deaths per year
Major risk factors for colon cancer are diet and smoking which contain
aromatic and heterocyclic amines

9. 9 Large intestine is approximately 1.5-m long and forms the colon
 The colon is 2–3 inch in diameter and its lumen is lined with mucus
 The physiology and the physical properties of the colonic contents also differ between the ascending, transverse,
descending, and sigmoidal colon
ANATOMY OF COLON
Descending
colon
Transverse
colon
Ascending
colon
Sigmoid
colon
 Variability in movement of food and dosage forms across the colon
 Intra and inter-subject variability in
the pH of GIT have been observed
between disease states, fasted/fed
states, sex, and age
 Factors such as viscosity and
volume of colonic fluids, presence of
microbial enzymes, and the colonic
metabolism.

10. 10INTESTINAL-COLONIC TRANSIT TIME
 Intestinal-colonic transit time plays an important role in the performance of CDDS
 Transit of dosage forms generally depends on the time of administration, presence/absence of food, and type of
dosage form
 Stubbs et al. studied the effect of dawn and dusk on the motility of dosage forms in the colon. The results showed that
colonic transit was delayed during sleep, and larger dosage forms, e.g., capsules transited faster compared to smaller
dosage forms, e.g., dispersed particles

11. 11
COLONIC FLUID VOLUME
 Colon has a high water-absorbing capacity and can absorb ~90% of the water entering the colon
 Colonic fluid volume is calculated to be in the range of 1–44 ml with an average volume of approximately 13 ml
 Due to this low volume of colonic fluids, the dissolution of drugs from the dosage forms becomes challenging
VISCOSITY OF COLONIC LUMINAL CONTENTS
 Because of higher water-absorbing capacity the viscosity of the colonic luminal contents is higher than upper GIT
contents
 The viscosity of the contents progressively increases as it transits from the ascending colon towards the descending
colon
 Influences the penetration of the drug into the disease-causing bacteria in the colon
 Mobility of bacteria in the colon has been shown to be dependent on the viscosity of colonic contents

12. 12
 GI tract plays host to over 500 distinct bacterial species
 Bacteria play pivotal roles in both digestion and intestinal health, including digestion and metabolism of fatty
acids, proteins and carbohydrates
 Majority of the intestinal microbiome resides in the anaerobic colon and fermentation of carbohydrates is the main
source of nutrition for this population
 Exclusive fermentation of non-starch polysaccharides by the colonic microbiome is exploited in formulations that
use non-starch polysaccharide coatings
 Variation in the composition of the microbiome between individuals, which is influenced by both genetic and
environmental factors, the dominant Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria species appear
to be consistent and represent the majority of the colonic flora
 Microbiome is exposed to temporal disruption (dysbiosis) by disease and medications (e.g. antibiotics), and is
influenced by factors such as diet, lifestyle and geographical distinctions
INTESTINAL MICROBIOME

13. 13
FORMULATION FACTORS
 Lower amount (1–44 ml) of colonic fluid available for dissolution
 The solubility and the dose of a drug become important factors for its colonic
bioavailability
 Highly potent drug budesonide (dose, 9 mg) has a lower aqueous solubility, it is absorbed
well in the colon
 Mesalamine has a significantly higher solubility (3.64 mg/ml) compared to budesonide
(0.24 mg/ml); however, it also has a significantly higher dose (4.8 g daily) which becomes a
rate-limiting factor for its colonic absorption
 Useris® and EntocortEC® are currently approved budesonide products for the treatment of
UC and CD, respectively
 Useris® is a multi-matrix (MMX)-based delayed-release tablets, which ensures the drug
release in the colon, while Entocort EC® is a capsule which releases the drug in the ileum
to treat CD

14. 14
CHANGES IN THE PHYSIOLOGY OF THE GI TRACT DURING
DISEASED CONDITION
 Mucosal inflammation in IBD causes pathophysiological changes, such as
 a disrupted intestinal barrier due to the presence of mucosal surface alterations, crypt distortions and ulcers
 increased mucus production and
 the infiltration of immune cells (e.g. neutrophils, macrophages, lymphocytes and dendritic cells)
 During relapse of IBD, patients may exhibit altered GI motility and diarrhoea, which in turn affects intestinal volume, pH
and mucosal integrity
 Active inflammation significantly alters the physiology of the GI tract which can affect the efficacy of conventional
approaches to colon targeted drug delivery
.

15. 15
TRANSIT TIME AND MICROBIALCONSIDERATIONS
Patients with UC have shorter colonic times (~24 h) compared to healthy subjects (~52 h)
Rana et al. showed that in patients with IBD, the orocecal transit time was delayed
Orocecal transit time (OCTT) has been shown to be delayed in both CD and UC patients
compared to healthy controls
Significantly faster OCTTs have been observed in IBD patients with the dysbiotic condition – small
intestinal bacterial overgrowth (SIBO)
Colonic transit is significantly faster in IBD patients, likely due to the diarrhoea that is a hallmark
of the disease
UC patients may exhibit transit times twice as rapid as a healthy individual

16. 16 Colonic pH is significantly lower in both UC and CD patients
 Intestinal pH is influenced by microbial fermentation processes, bile acid metabolism of fatty acids, bicarbonate
and lactate secretions, and intestinal volume and transit times
 Normal colonic pH ranges from 6.8 in the proximal colon and rises to 7.2 in the distal colon, this can significantly
vary in active UC patients from pH 5.5 to as low as 2.3
CHANGE IN COLONIC pH
 Composition of the intestinal biomass is altered in disease and is directly related to changes in microbial
metabolism
 Intestinal transit time and luminal pH increased fluid secretion and decreased reabsorption can dilute the
digestive enzymes that control intestinal transit to allow nutrient absorption
INTESTINAL VOLUME

17. 17
Conventional
approaches
New
approaches
 Colon targeted drug delivery system (CTDDS) should retard drug release in the stomach and small intestine but
allow complete release in the colon
 System will be exposed to a diverse range of gastrointestinal conditions on passage through the gut makes colonic
delivery via the oral route a challenging proposition
 Variety of approaches have been used and systems have been developed for the purpose of achieving colonic
targeting

18. 18
pH SENSITIVE
POLYMER
COATING
DELAYED
RELEASE
DRUG
DELIVERY
PRODRUGS
CONVENTIONAL APPROACHES

19. 19
pH SENSITIVE POLYMER
Use of pH dependent polymers is based on these differences in pH levels
Polymers described as pH dependent in colon specific drug delivery are insoluble at low
pH levels but become increasingly soluble as pH rises
Processes distribute the drug throughout the large intestine and improve the potentialof
colon targeted delivery systems

20. 20
pH sensitive
polymer
Drug
Stomach and small
intestine
Colon
Enteric polymers Optimum pH for dissolution
Polyvinyl acetate phthalate (PVAP) 5.0
Cellulose acetate trimelitate (CAT) 5.5
Hydroxypropyl methyl cellulose phthalate (HPMCP) >5.5
Methacrylic acid copolymer, Type C (Eudragit L100-55) >6.0
Cellulose acetate phthalate (CAP) (Aquateric) 6.0
Shellac 7.0
Contd..
Drug
release

21. 21DELAYED (TIME CONTROLLED RELEASE SYSTEM) RELEASE
 The duration of lag phase is controlled either by the weight or composition of the polymer layer
 Due to potentially large variations of gastric emptying time of dosage forms in humans colon arrival time of dosage
forms cannot be accurately predicted
 Not ideal to deliver drugs to the colon specifically for the treatment of colon related diseases
 The transit time of dosage forms in the small intestine is less variable i.e. about 3±1 hr
 The time-release function (or timer function) should work more efficiently in the small intestine as compared the
stomach

22. 22
Enteric
coating
Polymer
coating
Drug
molecule
Stomach Small intestine Colon
Drug release
Contd..

23. 23
 Prodrug is a pharmacologically inactive derivative of a parent drug molecule that requires spontaneous or enzymatic
transformation in vivo to release the active drug
 For colonic delivery, the prodrug is designed to undergo minimal hydrolysis in the upper tracts of GIT, and undergo
enzymatic hydrolysis in the colon there by releasing the active drug moiety from the drug carrier
 Metabolism of azo compounds by intestinal bacteria is one of the most extensively utilized approach, other linkages
susceptible to bacterial hydrolysis like amino acids, glucuronic acids, glucose, glactose, cellulose etc.
 Not a very versatile approach as its formulation depends upon the functional group available on the drug moiety for
chemical linkage
 Prodrugs are new chemical entities, and need a lot of evaluation before being used as carriers
PRODRUG

24. 24
Of the multitude of bacterial enzymes that are produced in colon, 2 main classesare:-
 The azo linkage exhibits a wide range of
pharmaceutical properties
 The azo compounds are extensively
treatment of rheumatoid arthritis.
metabolized by the intestinal bacteria
 Sulphasalazine, which was used for the
This
compound has an azo bond between 5-ASA
and sulphapyridine
 Naturally occurring polysaccharides
obtained from plant (guar gum, inulin),
animal (chitosan, chondrotin sulphate), algal
(alginates) or microbial (dextran) origin
 Polysaccharides broken down by colonic
microflora to simple saccharides and
considered as GRAS
AZOREDUCTASES POLYSACCHARIDASES
Contd..

25. 25
Azoreductases
Prodrug
5- amino
salicylic acid
Sulfapyridine
Contd..

26. 26
NEW APPROACHES
OSMOTIC
CONTROLLED
DELIVERY
COLAL® SYSTEM
INTESTINAL
PRESSURE-
CONTROLLED
COLON DELIVERY
CAPSULES
(PCDCS)
NANOPARTICULATE
SYSTEM
PULSINCAP
SYSTEMS
CODES™
TECHNOLOGY
AZO HYDROGELS
COLONIC DRUG
DELIVERY SYSTEM
BASED ON PECTIN
AND
GALACTOMANNAN
COATING

27. 27
• 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
• 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
• 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
OSMOTIC CONTROLLED DRUG DELIVERY (OROS-CT)

28. 28
Enteric
coating Orifice
Semipermeable
membrane
Drug
layer
Osmogen
layer
Stomach Small intestine Colon
Drug release
Contd..

29. 29
 A 54 mg tablet of Concerta (methylphenidate), which uses OROS technology.
 22% of the drug is contained in the red overcoat, while the remaining 78% is split between two drug layers of differing
concentration.
 The tablet uses an additional push layer that expands as water enters the tablet via the osmotic membrane.
 The drug is expelled via the laser-drilled hole visible on the left side of the tablet.

30. 30
Procardia XL
(Nifedipine)
Adalat OROS
(Nifedipine)
Cardura XL (Doxazosin)
Covera HS
(Verapamil)
Dynacirc CR (Isradipine) Glucotrol XL
(Glipizide)
Tegretol XR
(Carbamazepine)

31. INTESTINAL PRESSURE-CONTROLLED COLON DELIVERY
CAPSULES (PCDCs)
 PCDCs relies on the relatively strong peristaltic waves in the colon that lead to an increased luminal pressure
 Consists of a capsular shaped suppositories coated with a water-insoluble polymer ethyl cellulose
 Phase of raised pressure is very limited and it was reported that in healthy subjects this pressure can be as high as
110 mmHg with a duration of 14 s
 The performance of this system appears to be dependent on the capsule size and the thickness of ethyl cellulose
coating
PCDCs behaves like EC
balloon, the suppository
base liquefies at body
temperature
Upper g.i sufficient fluid
present in stomach and
small intestine
Water reabsorption in
colon viscosity of luminal
content increases
increased intestinal
pressure
31

32. 32Enteric coating
Ethyl cellulose
coating
Drug in
suppository base
matrix
Stomach
Suppository
base liquefies
due to body
temperature
Small
intestine
Colon
High pressure and
increment in
content volume
Drug
release
Contd..

33. 33
 Unique colon-specific drug delivery technology designed to avoid the inherent problems associated with pH or
time-dependent systems
 Exploit the advantages of certain polysaccharides that are only degraded by bacteria available in the colon with a
pH-sensitive polymer coating
 System exhibited the capability to achieve colon delivery consistently and reliably
 Acetaminophen release from CODES™ was investigated in 20 ml pH 6.8 buffer with or without 10% w/w rat caecal
contents
 In presence of rat caecal contents, acetaminophen release was essentially completed while no drug release was
observed in the medium containing no rat caecal contents
CODES™TECHNOLOGY

34. 34
Enteric
coating
Acid soluble
polymer
Polysaccharide
Stomach Small intestine
Colon
Organic acid
Drug
released
Contd..

35. COLONIC DRUG DELIVERY SYSTEM BASED ON PECTIN
AND GALACTOMANNAN COATING
 Technology was proposed by Lee et al. (1999) and Pai et al. (2000)
 Consists of a conventional tablet or capsule coated with two specific polysaccharides, namely pectin and
galactomannan
 Neither pectin nor galactomannan can be used as a drug carrier due to its high water solubility/ swelling
characteristics
 Solubility of the coating produced from the mixture of the two polysaccharides was found to predominantly depend
on the pH of coating solution
35
Strong, elastic and insoluble
in simulated gastric and
intestinal fluids.
Protect drug from being
released in the upper GI tract
pH˃7
Dissolved readily in the
simulated intestinal fluids
pH<7

36. 36the formation of an interjunction zone from conformational changes of polysaccharides
 Extent of film resistance to hydration and subsequent solubilization, the rate of film degradation by enzymes, and the
resultant drug release rate depend on the ratio of pectin to galactomannan
 Higher percentage of galactomannan results in decreased bacterial degradation in the colon and prolonged duration of
negligible drug release in the upper GI tract
 The site specificity of drug release was pharmacoscintigraphically confirmed in human subjects (Pai et al., 2000).
Compared with the combination of pectin and ethyl cellulose (Wakerly et al., 1996) or amylose and ethyl cellulose (Basit,
2000)
 Advantage of faster degradation in vivo since both pectin and galactomannan are readily degradable by microflora in the
colon
Contd..
 Complex between the two polysaccharides might be formed at pH 7 due to the hydrogen bonding, hydrophobic force, and

37. 37AZO HYDROGELS
 Presence of pH-sensitive monomers and azo cross-
linking agents in the hydrogel structure transit
 Through the GI tract, the swelling capacity of the
hydrogels increases as the pH increases, being highest
around pH 7.4
 The swelling characteristics of the hydrogels can be
further controlled by incorporating the hydrolyzable
moieties in the hydrogel structure

38. 38
 Upon arrival in the colon, the
hydrogels have reached a degree of
swelling that makes the cross-links
accessible to the enzymes
(azoreductase) or mediators
 The hydrogel network is
progressively degraded via the
cleavage of the cross-links, and the
drug entrapped is thus released
Contd..

39. 39COLAL® SYSTEM
 COLAL® is the proprietary drug delivery system Alizyme’s
 COLAL® involves a coating for drug pellets, tablets or capsules which is composed of ethylcellulose and a
specific form of amylose (derived from starch) called 'glassy amylose'
 Glassy amylose is not digested by human enzymes as the preparation moves down the GI tract, but is digested
by bacterial enzymes that are found only in the colon
 When the coated product reaches the colon, the coating is degraded, allowing the drug to be released

40. 40 Overcome the difficulty due to individual variation in conditions within the gastrointestinal (“GI”) tract and in the
transit time for the contents of the GI tract
 COLAL-PRED® is a proprietary gastrointestinal product developed by Alizyme for the treatment of ulcerative colitis
("UC") it contains approved generic steroid (prednisolone sodium metasulfobenzoate)
 Effective anti-inflammatory treatment for UC without the typical side effects of steroids
Therapeutic area Product Indication Stage of development
Gastrointestinal
COLAL-PRED® (Prometheus inUS) UC - treatment of active disease Phase II ongoing
COLAL-PRED® (TSD inJapan) UC - treatment of active disease Phase I ongoing
COLAL-PRED® UC - maintenance of remission Phase III ready
Contd..

41. 41PULSINCAP SYSTEM
Time-dependent systems are not always ideal for delivering drugs to the colon due to variability in
the gastric emptying time and the changes in gastrointestinal transit
The integration of a timed- release system with pH-sensitive properties can be beneficial in achieving
colon-targeted delivery
A pulsincap system is one example of a formulation that utilizes both these techniques release
system with pH-sensitive properties can be beneficial in achieving colon-targeted delivery

42. 42
Water
insoluble
body
Water
soluble cap
Acid
insoluble
film coat
Drug
formulation
Hydrogel
plug
Stomach Small intestine Colon
Drug
release
Contd..

43. 43
NANOPARTICULATE SYSTEM
 Nanotechnology in formulation design may further improve the efficacy of therapeutics by allowing inflammation-
specific targeting and uptake within the colon
 Nano-delivery systems have been designed to passively or actively target the site of inflammation
 More beneficial than conventional formulations, because their size leads to more effective targeting, better
bioavailability at diseased tissues and reduced systemic adverse effects
 Nano-delivery systems have been found to have similar or improved therapeutic efficacy at lower drug
concentrations in comparison to conventional formulations
 Additional strategies to enhance drug delivery to inflamed intestinal mucosa and achieve maximal retention time in
tissues are being explored

44. 44
IN VITRO EVALUATION
 Various mechanisms have been incorporated into colon-specific drug delivery systems
 Conventional dissolution testing proposed in USP appears unable to discriminate drug release from systems
with different triggering mechanisms
 Ideal dissolution testing should closely mimic the in vivo conditions with regard to pH, bacteria, types of
enzymes, enzymatic activity, fluid volume and mixing intensity
 Apparently, such dissolution specifications will be very difficult, if possible at all, to be standardized and
validated
 Several dissolution methodologies were reported in the literature for the testing of colon-specific drug
delivery systems

45. 45
 Conventional basket method has usually been conducted in different buffers for different periods of time to
simulate the GI tract pH and transit time that the colon-specific delivery system might encounter in vivo
 Takeuchi et al. assessed the dissolution of spray-dried lactose composite particles containing alginate-chitosan
complex as a compression coating in pH 1.2 and 6.8 buffer. Dry-coating showed excellent acid-resistance and
prolonged induction periods for drug release
 USP Dissolution Apparatus III (reciprocating cylinder) was employed to assess in vitro the performance of guar-
based colonic formulations
 Wong et al. evaluated several guar-based colonic formulations using apparatus III in simulated gastric fluid (pH
1.2), simulated intestinal fluid (pH 7.5) and simulated colonic fluids containing galactomannanase
 Drug release determined from the current USP dissolution setting is primarily qualitative in nature and may not
be correlated with the in vivo situation
Contd..

46. 46
 Overcome the limitation of conventional dissolution testing for evaluating colon-specific delivery systems
triggered by colon-specific bacteria, animal caecal contents including rats, rabbits and pigs have been utilized
as alternative dissolution medium
 Because of the similarity of human and rodent colonic microflora, predominantly comprising Bifidobacterium,
Bacteroides and Lactobacillus, rat caecal contents were more commonly used in the dissolution studies
Caecal contents were
diluted with phosphate-
buffered saline (PBS,
pH 7)
Conducted under CO2
or nitrogen to maintain
an anaerobic
environment
Drug release studies
were generally carried
out in sealed glass
vials at 37 °C

47. 47 Rubinstein et al. evaluated the indomethacin release from calcium pectinate tablets was in 100 ml pH 7 PBS with/
without 1.25% w/v rat caecal contents at 37 °C
 In the presence of rat caecal contents, 60.8 ± 15.7% of drug was released within 24 h in contrast to 4.9 ± 1.1%
drug release in the control medium
 Yang et al. investigated the acetaminophen release from CODES™ was in 20 ml pH 6.8 buffer with or without 10%
w/w rat caecal contents
 In presence of rat caecal contents, acetaminophen release was essentially completed while no drug release was
observed in the medium containing no rat caecal contents within the same time period
 Additional method to evaluate colon-specific drug delivery systems in vitro involves incubation of the delivery
system with commonly found colonic bacterium in a modular fermentor under anaerobic conditions

48. 48
 Five-step multichamber reactor (simulated human intestinal microbial ecosystem (SHIME)) was also fabricated
to simulate the human intestinal microbial ecosystem
 Each segment of human GI tract was represented with a reactor, with a medium containing starch, pectin, xylan
and arabinogalactan
 Schacht et al. investigated 3 polymeric drugs of 5-ASA namely poly(1-vinyl- 2-pyrrolidone-co-maleic anhydride)
(PVPMA), poly[N-(2-hydroxyethyl)-DL-aspartamide] (PHEA) and dextran, were evaluated in the SHIME reactor
Three polymeric prodrugs
of 5-ASA- PVPMA, PHEA
and dextran
Little or no hydrolysis in the
reactors representing
stomach and small intestine
Reactor simulating cecum
and colon, only dextran-5-
ASA exhibited drug release

49. 49
Conducted to evaluate the site specificity of drug release and to obtain relevant
pharmacokinetics information of the delivery system
Animal models have obvious advantages in assessing colon-specific drug delivery
systems
Human subjects are increasingly utilized for evaluation of this type of delivery systems
with visualization techniques such as γ-scintigraphy imaging
Different animals have been used to evaluate the performance of colon-specific drug
delivery systems, such as rats, pigs and dogs
Selection of an appropriate animal model for evaluation depends on its triggering
mechanism and system design
Guinea pigs are used for evaluating glucoside and glucuronate conjugated prodrugs and
azoreductase activity in GI tract is similar between rats and human subjects
IN VIVO
EVALUATION
Contd..

50. 50
PATENTS REPORTED IN THE FIELD OF COLONIC DRUG DELIVERY SYSTEM

51. 51
MARKETED
FORMULATIONS

52. 52
CONCLUSION
Colonic region of the GIT has become an increasingly important site for drug delivery and
absorption
Successful colon drug delivery requires the triggering mechanism that only respond tothe
physiological conditions of colon
Uncertainty of current dissolution methods in establishing possible in vitro/in vivo correlation
Challenges remain for pharmaceutical scientists to develop and validate a dissolution method
that incorporates the physiological features of the colon

53. 53