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Colon targeted drug delivery systems
1. ONTARGET
Targeted Drug Delivery Systems
Dr. Gajanan S. Sanap M.Pharm.,Ph.D
Department of Pharmaceutics
Ideal College of Pharmacy and Research
Kalyan 421- 306
COLON TARGETED DRUG DELIVERY
2. ī
ī Introduction
ī Anatomy of colon
ī Criteria of drug selection
ī Approaches of colon targeting
ī EVALUATION
īReference
CONTENTs
3. INTRODUCTION
Targeted drug delivery systems:
īļ The major goal of any drug delivery system is to supply a therapeutic
amount of drug to a target site in a body.
īļ Targeted drug delivery implies selective and effective localization of
drug into the target at therapeutic concentrations with limited access
to non target sites.
īļ A targeted drug delivery system is preferred in drugs having
instability, low solubility and short half life,
4. Definition:-
Colon drug delivery system refers to targeted delivery of drug in to the
lower parts of GI tract , mainly large intestine.
Targeted delivery of drugs to the colon is usually to achieve one or
more of four objectives.
īTo reduce dosing frequency
īTo delay delivery to the colon to achieve high local concentrations
in the treatment of diseases of the distal gut,
īTo delay delivery to a time appropriate to treat acute phases of
disease (chronotherapy),
īTo deliver to a region that is less hostile metabolically, e.g., to
facilitate absorption of acid and enzymatically labile materials,
especially peptides.
5. ī Oral route is considered to be most convenient for administration of
drug to patient.
ī Colon is used as site of Targeted drug delivery.
ī Colon was considered as a BLACK-BOX , as most of the drug are
absorbed from the upper part of the GI tract.
ī Prime objective-Beneficial in the treatment of colon diseases.
īŧIncrease the pharmacological activity.
īŧReduce dosing & side effects.
īŧPrevent drug from degradation.
6. īAs most of the conventional drug delivery systems for treating colon
disorders such as inflammatory bowel diseases, infectious diseases and
colon cancer are failing as the drugs don't reach the site of action in
appropriate concentration.
īThus an effective and safe therapy of these colonic disorders using
site specific drug delivery system.
ī The therapeutic advantages of targeting drug to the diseased organ
include,
a)Delivery of drug in its intact form as close as possible to the target
site.
b)The ability to cut down the conventional dose.
c) Reduced incidence of adverse side effects.
WHY COLON TARGETED DRUG DELIVERY IS NEEDED?
7. īIn recent times the colon-specific delivery systems(CSDDS) are also
gaining importance for the systemic delivery of protein and peptide
drugs . This is because,
i)as the peptide and protein drugs are destroyed and inactivated in acidic
environment of stomach or by pancreatic enzymes (or) by parenteral
route which is inconvenient and expensive.
ii) Due to the negligible activity of brush border membrane peptidase
activity and less activity of pancreatic enzymes the colon is considered as
the most suitable site.
8. ADVENTAGES
ī The site specific delivery of drug to lower part of GIT, for
localized treatment of several colonic diseases. (ulcerative
colitis, Chron's disease, carcinomas and infections)
ī Prevent drug from degradation
ī Ensure direct treatment at disease site.
ī Suitable absorption site for Protein & Peptide drug.
ī Used to prolong the drug therapy.
ī Improved drug utilization.
9. īMultiple manufacturing steps.
īMicroflora affects activity of drug via metabolic degradation of the
drug.
īBioavailability of drug may be low due to potentially binding of
drug in a nonspecific way to dietary residues, intestinal secretions,
mucus or faecal matter.
īNon availability of an appropriate dissolution testing method to
evaluate the dosage form in-vitro.
īDrug should be in solution form before absorption and there for
rate limiting step for poor soluble drugs.
Limitations / Challenges/Difficulties
10. ī Substantial variation in gastric retention time may
affect drug delivery.
ī Diseased condition may affect the colonic transit
time and drug release profile.
ī pH level of colon may vary between individuals
due to disease, state and temperature of food
consumed.
11. Application
īļIn local colonic pathologies
īļSystemic delivery of protein and peptide
īļPotential site for the treatment of diseases sensitive to
circadian rhythms (asthma, angina and arthritis)
īļFor the drugs that are absorbed through colon such as
steroids (âĻ.efficacy..)
īļFor the treatment of disorders like IBS, colitis, crohnâs
disease (âĻwhere it is necessary to attain high concentration
of drugs)
12. Table 1. Colon targeting diseases, drugs and sites
Targetsites Disease conditions Drugand activeagents
Topical action Inflammatory Bowel
Diseases, Irritable bowel
disease and Crohnâs 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
17. Colon Cancer
īColon and rectum cancer - 10% in men and 11% women
ī >55,000 Total Colorectal Cancer Deaths
18.
19. Anatomy & physiology of colon
īThe GI tract is divided into stomach, small intestine & large
intestine.
īThe colon itself is made up of the caecum, ascending colon,
hepatic flexure, transverse colon, splenic flexure, descending
colon, sigmoid colon.
īIt is about 1.5 m long.
īAlthough it varies in diameter from approx 9 cm in caecum
& 2 cm in sigmoid colon.
īThe wall of colon is composed of 4 layers: serosa,
muscularis externa, sub mucosa & mucosa.
īSerosa consists of areolar tissue, muscularis externa
composed of an inner circular layer of fibers, sub mucosa is
layer of connective tissue, mucosa is divided into epithelium
lamina propria & muscularis mucosae
20.
21. Function of colon
ī Formation of suitable environment for colonic
microorganism.
ī Act as storage reservoirs of waste matter.
ī Removal of content of colon at proper time.
ī Absorption of potassium ion & water from
lumen, concentrating fecal content & secretion
& excretion of potassium & bicarbonates.
22. ī Gastrointestinal Transit --
ī Gastric emptying of various dosage form is highly
inconsistant & depends primary on whether the subject is
fed or fasting & properties of dosage form.
ī The arrival of dosage form in colon is determined by
rate of gastric emptying & intestine transit time.
Intestinal transit time
Organ Transit time (hrs)
Stomach <1 (fasting)
>3 (fed)
Small intestine 3-4
Large intestine 20-30
23. Factors to be considered for colonic drug delivery
1. pH in the colon:
īŧ pH of the GI tract is subjected to both inter & intra subject
variation.
īŧ On entry in to the colon, the pH dropped to 6.4 . The pH in
the mid colon & the left colon is 6.0- 7.6
Location pH
Oral cavity 6.2-7.4
Esophagus 5.0-6.0
Stomach Fasted condition 1.5-2.0
Fed condition 3.0-5.0
Small intestine Jejunum 5.0-6.5
Ileum 6.0-7.5
Large intestine Right colon 6.4
Mid & left colon 6.0-7.6
24.
25. 2. Gastrointestinal transit:
īŧGastric emptying of dosage forms is highly variable &
depends primarily on whether the subject is fed or fasted.
īŧThe arrival of an oral dosage form at the colon is determined
by the rate of gastric emptying & the small intestinal transit
time.
īŧThe transit time of dosage form in GIT:
Organ Transit time (hrs)
Stomach <1 (fasting), >3 (fed)
Small intestine 3-4
large intestine 20-30
26. 3. Colonic microflora:
īŧMany compounds taken orally are metabolized by gut
bacteria.
īŧDrug release depends on enzymes that are derived from
microflora present in colon.
īŧThese enzymes are used to degrade coatings/matrices as well
as to break bonds between an inert carrier and an active agent
resulting in the drug release from the formulation.
īŧImportant metabolic reactions carried out by intestinal
bacteria : hydrolysis, reduction, dehydroxylation,
decarboxylation, dehalogenation, deamination, acetylation,
esterification.
27. Drug absorption in the colon
īŧDrugs are absorbed passively by either paracellular or
transcellular route.
īŧTranscellular absorption involves the passage of drugs through
cells.(Lipophilic drug)
īŧParacellular absorption involves the transport of drug through
tight junction between cells. ( Hydrophilic drug)
īŧThe colon may not be the best site for drug absorption since the
colonic mucosa lacks well defined villi as found in the small
intestine.
īŧThe colon contents become more viscous with progressive
absorption of water as one travels further through the colon. This
causes a reduced dissolution rate, slow diffusion of drug through
the mucosa.
28. Role of absorption enhancers
īŧThe permeability of drugs can be modified by the use of
chemical enhancers.
īŧThese enhancers increase transcellular & paracellular
transport through one of the following mechanism:
1. By modifying epithelial permeability via denaturating
membrane proteins.
2. By reversibly disrupting the integrity of lipid bilayer of
colon.
Category Example
NSAIDs Indomethacin
Calcium ion chelating agent EDTA
Surfactants Polyoxyethylene lauryl ether
Bile salts Glycocholate
Fatty acids Sodium caprylate
Mixed micelles Oleic acid glycocholate
29. ī
ī Drugs used for local effects in colon against GIT diseases.
ī Drugs poorly absorbed from upper GIT.
ī Drugs for colon cancer.
ī Drugs that degrade in stomach and small intestine.
ī Drugs that undergo extensive first pass metabolism.
ī Drugs for targeting.
Criteria of drug selection
30. Pharmaceutical Approaches for Targeting Drugs
to Colon
ī pH sensitive systems
ī Microbially triggered system
âĻ Prodrugs
âĻ Polysaccharide based systems
ī Timed release systems
ī Osmotically controlled drug delivery systems
ī Pressure dependent release systems
ī An oral colonic delivery system should retard drug release in the
stomach and small intestine but allow complete release in the
colon.
ī A variety of strategies has been used and systems have been
developed for the purpose of achieving colonic targeting .
31. Approaches to colon specific drug delivery
1. Coating with pH dependent polymers:
īļ The underlying principle of this approach has been employment of
polymers that are able to withstand the lower pH values of the
stomach, but that disintegrate and release the drug as the pH in the
small bowel increases.
īļSelection of enteric polymer dissolving at pH 7 is likely to cause
drug release in terminal small bowel.
īļThe 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.
īļThe polymers described as pH dependent in colon specific drug
delivery are insoluble at low pH levels but become increasingly
soluble as pH rises.
īļThese processes distribute the drug throughout the large intestine
and improve the potential of colon targeted delivery systems.
32.
33. Examples: Cellulose Acetate Phthalate (CAP)
CAP is a white free-flowing powder. It is insoluble in water, alcohols,
and chlorinated hydrocarbons, but soluble in acetone and its mixtures
with alcohols, ethyl acetateâIPA mixture.
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
Table. pH of commonly used enteric polymers.
34. ī Cellulose Acetate Phthalate:
ī Methacrylic Acid Copolymers:
ī These are anionic copolymers and are very commonly utilized for
enteric coating, including application in colonic delivery.
ī
ī Eudragit L
35. Shellac:
ī Shellac is a material of natural origin used for enteric coatings. It is
a purified resinous secretion of the insect Laccifer lacca.
Hydroxypropyl Methylcellulose Phthalate (HPMCP):
ī HPMCP is a white powder or granular material. It is a more
flexible polymer than CAP. Commercially, the available forms are
HPMCP-50 and HPMCP-55.
37. ī The microflora of the colon is in the range of 1011 -1012 CFU/ mL,
consisting mainly of anaerobic bacteria, e.g. bacteroides,
bifidobacteria, eubacteria, clostridia, enterococci, enterobacteria and
ruminococcus etc.
ī Microflora produces a vast number of enzymes like glucoronidase,
xylosidase, arabinosidase, galactosidase, nitroreductase, azareducatase,
deaminase, and urea dehydroxylase.
ī Presence of the biodegradable enzymes only in the colon, the use of
biodegradable polymers for colon-specific drug delivery.
ī These polymers shield the drug from the environments of stomach and
small intestine, and are able to deliver the drug to the colon.
Microbially Triggered Drug
Delivery to Colon
38. ī A Prodrug is a pharmacologically inactive derivative of a parent
molecule that require some form of transformation in vivo to release the
active drug at the target site.
ī This approach involves covalent linkage between the drug and its carrier.
ī Biotransformation is carried out by a variety of enzymes, mainly of
bacterial origin, present in the colon. The enzymes that are mainly
targeted for colon drug delivery include azoreducatase-galactosidase, β-
xylosidase, nitroreductase, glycosidase deaminase, etc.
PRODRUG
ī§For colonic delivery , prodrug is designed to undergo minimal
hydrolysis in upper tracts of GIT & undergo enzymatic hydrolysis in
colon there by releasing the active drug moiety from drug moiety.
ī§Metabolism of azo compound by intestinal bacteria is one of most
extensively studied bacterial metabolic process.
39. ī The azo linkage exhibits a wide
range of thermal, chemical,
photochemical and pharmaceutical
properties.
ī The azo compounds are
extensively metabolized by the
intestinal bacteria.
ī Sulphasalazine, which was used
for the treatment of rheumatoid
arthritis. This compound has an
azo bond between 5-ASA and
sulphapyridine.
ī Include naturally occurring
polysaccharides obtained from
plant (guar gum, inulin), animal
(chitosan, chondrotin sulphate),
algal (alginates) or microbial
(dextran) origin.
ī The polysaccrides can be broken
down by the colonic microflora to
simple saccharides. Therefore,
they fall into the category of
âgenerally regarded as safeâ
(GRAS).
AZOREDUCTASES POLYSACCHARIDASES
Of the multitude of bacterial enzymes that are produced in colon, 2
main classes are:-
40. 40
Prodrugs
Drug Carrier Molecule
Enzymatic stimuli in the biological
environment of the GIT breaks the bond
Concept
of
prodrug
s
Prodrugs
Drug Carrier Molecule
Concept
of
prodrug
s
Prodrugs
Drug Carrier Molecule
Concept
of
prodrug
s
Prodrugs
Drug Carrier Molecule
Concept
of
prodrug
s
42. Prodrugs: Example,
īŧSulfasalazine is mainly used for the treatment of inflammatory
bowl diseases.
īŧChemically it is 5-amino salicylic acid (5-ASA) coupled with
sulphapyridine by azo bonding.
īŧOn reaching the colon, the azo bond is reduced by
azoreductases to 5-ASA & sulphapyridine.
īŧThe active moiety is 5-ASA & sulphapyridine acts as carrier
to deliver 5-ASA in colon.
43. Azo polymeric new drug
ī In which use of polymers as drug carriers for drug
delivery to colon .
ī Synthetic, naturally, sub-synthetic polymers used form
colon targeted polymeric prodrug with azo linkage
between polymer & drug moiety.
ī The various azo polymers are evaluated for coating
materials over drug core. These are susceptible to
cleavage by azo reductase enzyme.
ī Coating of protein & peptide drug capsules
crosslinked with azoaromatic group Polymer to
protect drug from degradation in stomach & small
intestine. In colon azo bonds reduced & drug is
released 43
44. 1)Azo bond conjugate:-
Azoreductase enzyme produced in colon by colonic
bacteria which degrades azo bond.
This principle is utilized in preparation of prodrug
derivative of active drug for targeting in colon.
īąSulphasalazine(SASP) is prodrug of 5-ASA. It is conjugated
with sulphapyridine through azo bond.
īąSulphasalazine was introduced for the treatment of rheumatoid
arthritis and anti-inflammatory disease.
45. Carrier moiety conjugated
with 5-amino salicylic acid
Prodrug of 5-amino
salicylic acid
p-aminohippurate (4-amino
benzoyl glycine)
ipsalazine,
p- 4-amino benzoyl-β-
alanine
balsalazine
p-aminobenzoate HB-313
nonabsorbable
sulphanilamide ethylene
polymer
poly-ASA
a dimer representing two
molecules of 5-ASA that are
linked via an azo bond
olsalazine (OSZ)
45
46. Polysaccharide based delivery system
īPolysaccharides offer an alternative substrate for the
bacterial enzymes present in the colon.
īMost of them are hydrophilic in nature.
īNatural polysaccharides are either modified or mixed
with water insoluble polymers.
46
47. Polysaccharides as carriers:
īŧThe colonic microflora secretes a number of enzymes that are
capable of hydrolytic cleavage of glycosidic bonds.
īŧThese include β-d-glucosidase, β-dgalactosidase, amylase,
pectinase, xylanase, Îą-d-xylosidase, and dextranases.
īŧNatural polysaccharides like pectin & inulin are not digested in
stomach & small intestine but are degraded in colon by resident
bacteria.
īŧThe bacteria converts polysaccharides to gases such as methane,
carbon dioxide, hydrogen & to short chain fatty acids.
īŧThese polysaccharides thus have the potential as non-toxic
carriers for colon specific drug delivery.
52. Time release dosage forms:
īNonbiodegradable polymers are used.
īThey are generally nonspecific with respect to pH-solubility characteristics and
the employment of these polymers as carrier matrices for colonic delivery often
utilizes a time-dependent mechanism.
ī This provides an initial lag phase of low or no release during transit through
the upper gastrointestinal tract.
ī The lag time usually starts after gastric emptying because most of the time-
controlled formulations are enteric coated.
ī The enteric polymer coat prevents drug release in the stomach.
ī Drug release from these systems is not pH dependent.
ī Various polymers used are: polyacrylates, methylcellulose, HPMC, CMC etc.
54. īąThis system, first described by Shah & co-workers, uses lag time to
achieve colon delivery.
īąSystem consist of 3 main parts: An outer enteric coat, inner
semipermeable polymer membrane, and a central core having swelling
excipients and an active component.
īąThe outer enteric coating prevents drug release until the tablet reaches
the small intestine.
īąIn the small intestine, the enteric coating dissolves allowing
gastrointestinal fluids to diffuse through the semipermeable membrane
into the core.
īąThe core swells until after a period of 4â6 h, when it bursts, and releases
the active component in the colon.
63. īļTIME CLOCKÂŽ SYSTEM
ī Solid dosage form coated
with lipid barriers containing
carnauba wax and bees wax
along with surfactants.
ī Further coated with enteric
coating polymer to prevent
premature drug release, but
the release is independent of
pH or digestive state of the
gut
Enteric coating
Wax coating with
surfactant
Drug core
64. īļCOLAL-PREDâĸ
īPellets containing the drug (prednisolone
metasulphobenzoate) with a coating of
ethylcellulose and a specific form of amylose
(derived from starch).
īAfter completion of succsesful phase I and II
trials âAlizymeâ obtained approval for Phase III
clinical trial of COLAL-PREDTM in maintenance
of remission of ulcerative colitis.
65. īPatient compliance and treatment efficacy
īUseful in treatment of ulcerative colitis, crohn's disease,
irritable bowel syndrome and carcinomas
īLow dose is required ,so less side effect
īUsed for local and systemic action
īGastric irritation can be avoided
66. īļDisadvantages
īThere is less fluid in colon than in small intestine and
hence, dissolution is a problem for water soluble drugs.
īBinding of drug to dietary residues, intestinal
secretions etc., reduce concentration of free drugs.
īSome micro flora may degrade the drug.
īSmall luminal surface area and relative tightness of
tight Junctions in colon, delay the systemic absorption.
īOnset of action is slow.
67. īļApplications
LOCALACTIONS
1. Ulcerative colitis.
2. CHRON'S disease.
3. Irritable bowel syndrome.
4. Metastatic human colon cancer.
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.
68. īThe 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.
īThe 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.
īFor 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.
īOROS-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 (ORDS-CT)
69.
70. Delivery port
Osmet pump
Depend up on the osmotic pressure
exerted by osmogens on drug
compartment with which though drug
get released slowly through the
orifice.
71. OROS-CT (Alza corporation)
īąImmediately after the OROS-CT is swallowed, the gelatin capsule
containing the push-pull units dissolve
īą Because of its enteric coating, each push-pull unit is prevented
from absorbing water in the acidic environment.
īąAs the unit enter the small intestine, the coating dissolve in this
higher pH (pH >7), water enters the unit, causing the osmotic push
compartment to swell and concomitantly creates a flowable gel in
the drug compartment.
īąSwelling of the osmotic push layer forces drug gel out of the
orifice.
72. MARKETED PRODUCTS
Sr.
no.
Marketed
name
Company
name
Disease Drug content
1) Mesacol tablet Sun pharma,
India
Ulcerative
colitis
Mesalamine
2) SAZO Wallace , India Ulcerative
colitis, crohnâs
disease
Sulphasalazin
e
3) BUSCOPAN German
remedies
Colonic
motility
Hyoscine
butyl bromide
4) Entofoam Cipla, India Ulcerative
colitis
Hydrocortison
e acetate
73. For evaluation, not any standardized evaluation technique is available
for evaluation of CDDS because an ideal in vitro model should posses
the in-vivo conditions of GIT such as pH, volume, stirring, bacteria,
enzymes, enzyme activity, and other components of food.
These conditions are influenced by the diet, physical stress, and these
factors make it difficult to design a standard in-vitro model.
EVALUATION
1. In vitro dissolution study
2. In vitro enzymatic degradation test
3. Relative colonic tissue exposure
4. Relative systemic exposure to drugs
5. ī§-Scintigraphy
6. Magnetic moment imaging study
7. Drug delivery index
8. High frequency capsule
74. 1. In vitro methods:
ī The ability of the coats/ carriers to remain in the physiological
environment of the stomach and small intestine is generally
assessed by conducting drug release studies in,
âĸ Drug release study in 0.1 N HCl for 2 hours (mean gastric emptying
time)
âĸ Drug release study in phosphate buffer for 3 hours (mean small
intestine transit time PH 6.8)
īThese dissolution studies can be carried out by using paddle or basket
or flow through dissolution apparatus.
75. IN-VITRO DISSOLUTIONTEST
ī Dissolution of CDDS is usually complex, dissolution
Describe in USP
ī Disso. Carried out by conventional basket method.
ī Dissolution tests for CDDS in different media simulating pH
condition & times likely to be encountered at various
location in GI tract.
ī Following media were used-
pH 1.2 to simulate gastric fluid.
pH 6.8 to simulate jejunal region of small intestine.
pH 7.2 to simulate ileum segment.
Enteric coated CDDS studied in gradient disso. Study in 3
buffer systems. 2 hr at pH 1.2, then 1 hr at pH 6.8& finally
at pH 7.4
75
76. BioDis-III (Apparatus III)
âĸ Ideal for the dissolution profiling of extended release
dosage forms.
âĸ It is designed to meet or exceed current USP specification.
âĸ It used a reciprocating motion to dip the inner tube into
media.
âĸ At the designated time, the entire row of inner tubes
raises and moves to the next row of media.
77. Bio-Dis III
âĸ Capable of running unattended upto 6 days and can store upto 25
programms.
âĸ 7 sample tubes which automatically traverse upto 6 rows of
corresponding outer tubes filled with different media.
âĸ With accessories, the appropriate media volume can vary from 100,
300 ml (USP) or 1000 ml.
BioDis III
78. In vitro enzymatic degradation test
Method 1:
Drug release in buffer medium containing enzymes(e.g.pectinase, dextranase) or
rat or guinea pig or rabbit decal contents
Amount of drug release in particular time directly proportional to the rate of
degradation of polymer carrier.
Method 2:
Incubating carrier drug system in fermenter
Suitable medium containing colonic bacteria (streptococcus faecium or B.ovatus)
Amount of drug released at different time intervels determined.
B R Nahata College of Pharmacy
Mandsaur (M.P.)
79. 2 In vivo methods:
īąAnimal models
īRats, mice, pigs and dogs animal models were reported for colon
targeted drug delivery systems.
īFor simulating the human physiological environment of the colon,
appropriate animal model selection is depends on its approach and
design of system.
īFor example, guinea pigs have glycosidase and glucuronidase activities
in the colon and digestive anatomy and physiology is similar to that of
human, so they are appropriate in evaluating prodrugs containing
glucoside and glucuronate conjugated for colonic delivery.
80. īTechniques which are used for monitoring the in vivo behavior of
colon targeted drug delivery are
String technique,
Endoscopy,
Radiotelemetry,
Roentegenography,
Gamma scintigraphy.
String technique : In these studies, a tablet was attached to a
piece of string and the subject swallowed the tablet, leaving the free
end of the string hanging from his mouth.
īAt various time points, the tablet was withdrawn from the stomach
by pulling out the string and physically examining the tablet for the
signs of disintegration.
81. Endoscope technique:
īIt is an optical technique in which a fiber scope (gastro scope) is
used to directly monitor the behavior of the dosage form after
ingestion.
īThis method requires administration of a mild sedative to facilitate
the swallowing of the endoscopic tube. The sedative alter the gastric
emptying and GI motility.
Radiotelemetry :
īThis technique involves the administration of a capsule that consist
of a small pH probe interfaced with a miniature radio transmitter
which is capable of sending a signal indicating the pH of the
environment to an external antenna attached to body of the subject.
īSo it is necessary to physically attach the dosage form to the capsule
which may effect the behaviour of the dosage form being studied.
82. Reoentgenography :
īThe inclusion of a radio-opaque material into a solid dosage form
enables it to be visualized by the use of X-rays.
īBy incorporating Barium sulphate into a pharmaceutical dosage form,
it is possible to follow the movement, location, and the integrity of the
dosage form after oral administration by placing the subject under a
fluoroscope and taking a series of X-rays at a various time points.
Gamma scintigraphy
īThe most useful technique, to evaluate the in vivo behavior of dosage
forms in animals and humans is external scintigraphy or gamma
scintigraphy
īIt requires the presence of a gamma emitting radio active isotope in the
dosage form that can be detected in vivo by an external gamma camera.
The dosage form can be radio labeled using conventional labeling or
neutron activation methods.