GASTRO-RETENTIVE DRUG

DELIVERY SYSTEM

By:
Mr. Lalit Rana
M.Pharm (Pharmaceutics)
 CONTENTS
 Introduction
 Gastrointestinal tract physiology
 Potential candidates for GRDDS
 Factors affecting GRDDS
 Merits and Demerits
 Approaches for GRDDS
 Methodology
 Evaluation parameters
 Applications
 Marketed formulations
 Conclusion
 Reference
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 INTRODUCTION
 Gastroretentive drug delivery is an approach to prolong
gastric residence time, there by targeting site-specific drugs
release in the upper gastrointestinal tract (GIT) for local or
systemic effects. It is obtained

by retaining dosage form into

stomach and by releasing the

in controlled manner.

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 GASTROINTESTINAL
TRACT
PHYSIOLOGY

Migrating myoelectric cycle 4

 POTENTIAL CANDIDATES
FOR GRDDS
 Drugs acting locally in the stomach.
E.g. Antacids and drugs for H. Pylori viz.,
Misoprolol.
 Drugs that are primarily absorbed in the stomach.
E.g. Amoxicillin
 Drugs that is poorly soluble at alkaline pH.
E.g. Furosemide, Diazepam, Verampil, etc.
 Drugs with a narrow absorption window.
E.g. Cyclosporine, Levodopa, Methotrexate etc.
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 Drugs which are absorbed rapidly from the GI
tract.

E.g. Metronidazole, tetracycline.

 Drugs that degrade in the colon.

E.g. Ranitidine, Metformin.

 Drugs that disturb normal colonic microbes.

E.g. Antibiotics against H. Pylori.

 Drugs with less half life.

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 DRUG CANDIDATES NOT
SUITABLE FOR GRDDS
 Drugs that have very limited acid solubility.

E.g. Phenytoin, etc.

 Drugs that suffer instability in the gastric environment.

E.g. Erythromycin, etc.

 Drugs intended for selective release in the colon.

E.g. 5-Amino salicylic acid and corticosteroids, etc.

 Drugs having extensive first pass metabolism.

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 FACTORS AFFECTING THE
GRDDS
 Density
 Size and Shape of the dosage form
 Single or Multi unit formulation
 Age
 Gender
 Body posture
 Frequency of intake
 Diseased state of an individual
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 MERITS
 Improved drug absorption.
 Enhanced bioavailability.
 Reduced dose frequency.
 Controlled drug delivery of drugs.
 Minimized mucosal irritation.
 Local action.
 Better patient compliance.
 Site specific drug delivery.
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 DEMERITS
 Drugs that cause gastric lesions. E.g. NSAIDs.
 Drugs that undergo first pass metabolism. E.g.
Nifedipine.
 Drugs that have very limited acid solubility and stability.

E.g. Phenytoin.
 Drugs that degrade in acidic environment.
 Drugs which are well absorbed along the entire GIT.
 Requires high levels of fluids in stomach.
 Requires presence of food to delay gastric emptying.
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11
 APPROACHES TO GASTRIC
RETENSION
 High density system
 Low density system
 Mucoadhesive system
 Raft forming system
 Swellable system
 Superporous hydrogels
 Self unfolding systems

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13
 A. FLOATING DRUG
DELIVERY SYSTEMS
Floating drug delivery systems have

a bulk density lower than gastric

fluids and thus remain buoyant in the

stomach for prolonged period of time,

without affecting the gastric emptying rate. While the system

is floating on the gastric contents, the drug is released

slowly at a desired rate from the system. This type is also

called as hydro dynamically balanced system (HBS).

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 MECHANISM OF
FDDS
FDDS has a bulk density less than gastric fluids and soremain
buoyant in the stomach without affecting the gastric
emptying rate for a prolonged period of time.
F= buoyancy- gravity = (Df-Ds)gv
Where,F= total vertical force,
Df= fluid density,
Ds= object density,
v = volume,
g = acceleration
due to
gravity.

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TYPES OF FLOATING
SYSTEM

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 Effervescent system: This are low density FDDS is
based on the formation of CO2 within the device following
contact with the body.

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 Non effervescent system:
This system use a gel forming
(or) swellable cellulose type of
Hydrocolloids,
polysaccharide, matrix
forming polymer like
polycarbonate, polystyrene
and polymethacrylate. One of
the formulation methods
involves the mixing of the
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This hydrocolloids swell in contact with gastric fluid after
oral administration and maintains integrity of shape and a
bulk density barrier, the air trapped by swollen polymer
confer buoyancy to the dosage forms.

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 RAFT FORMING
SYSTEM
 This system is used for delivery of antacids and drug
delivery for treatment of gastrointestinal infections and
disorders.

 The mechanism involved

in this system includes the

formation of a viscous

cohesive gel in

contact
with gastric fluids, 20
 MICROPOROUS COMPARTMENT
SYSTEM
This technology is based on the

encapsulation of a drug

reservoir inside a microporous

compartment with pores

along

its top and bottom walls. The peripheral wall of the drug

reservoir compartment is completely sealed to prevent

any direct contact of gastric surface with the undissolved

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drug.
 ALGINATE
BEADS
 It is prepared by dropping sodium alginate solution into
solution of calcium chloride, causing the precipitates of
calcium alginate.
 Freeze dry in liquid nitrogen at -40ºc for 24 hrs.
 Formation of porous system which can maintain a floating
force over 12 hrs.

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 MICROSPHERE
S
 Microballons/ hollow loaded with
drugs
microspheres prepared by solvent solvent diffusion/
evaporation or evaportaion methods.

 Buoyancy and drugsrelease depends on quality of polymers,

plasticizer polymer and solvents used.

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 MAGNETIC
SYSTEM
 This approach to enhance the GRT is based on the simple
principle that the dosage form contains a small internal
magnet, and a magnet placed on the abdomen over the
position of the stomach.
 Although magnetic system
seems to work, the external
magent must be positioned
with a degree of precision
that might compromise
patient compliance. 24
 B. HIGH DENSITY
SYSTEM
 Gastric contents have a density close to water.
 A density close to 2.5g/cm3 is necessary for

significant prolongation of gastric

residence time.
 The commonly used excipients in high density system includes
barium sulphate, zinc oxide, iron powder, and titanium dioxide.
 The major drawback with such systems is that it is technically
difficult to manufacture them with a large amount of drug (>50%)
and to achieve the required density.

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 C. BIOADHESIVE OR
MUCOADHESIVE
SYSTEM
 Bio/ muco-adhesive are those which bind to the gastric
epithelial cell surface or mucin and serve as a potential
means of extending the GRT of drug delivery system (DDS)
in the stomach,by interesting the intimacy and duration of
contact of drug with the biological membrance.
 The basis of adhesion in that a dosage form can stick to the
mucosal surface by different mechanism. These mechanism
are:

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1. The wetting theory.

2. The diffusion theory.

3. The absorption theory.

4. The electron theory.

POLYME
R

MUCUS
MEMBRANE

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 D. SWELLABLE SYSTEMS
 These are dosage forms which after swallowing, swell to an
extent that prevents their exit from the pylorus. As a result,
the dosage form is retained in stomach for a long period of
time. These systems may be named as “plug type system”,
since they exhibit tendency to remain logged at the pyloric
sphincter.

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 E. SUPERPOROUS HYDROGELS

a) Superporous hydrogel in dry state.

b) Superporous hydrogel in water swollen state.
c) On the right, schematic illustration of the transit or superporous
hydrogels
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 Swellable agents with pore size ranging between 10nm and
10µm, absorption of water by conventional hydrogel is very

slow process and several hours may be needed to reach as

equilibrium state during which premature evacuation of the
dosage form may occur.
 Superporous hydrogels swell to equilibrium size with in a
minute, due to rapid water uptake by capillary wetting
through numerous interconnected open pores.

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 F. SELF UNFOLDING SYSTEM
 These systems are made of biodegradable polymers and are
capable of being mechanically increased in size relative to
the initial dimensions.
 After being swallowed, these dosage forms swell to a size
that prevents their passage
though rough the pylorus
and therefore, the dosage
form is prone to be retained
in the stomach for a long
period of time.
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 METHODOLOGY
 Direct compression method
 Melt granulation technique
 Effervescent technique
 Spray drying technique
 Solvent evaporation technique
 Wet granulation technique
 Ionotropic gelation technique

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 EVALUATION PARAMETERS
Pre- compression test:
•Post compression test:
• Size and shape
• Thickness and diameter
• Particle size
• Hardness and friability
• Density
• Weight variation test
• •
floating Specific
time gravity

• • uniformity
Content Flow properties
• Dissolution test
• Mucoadhesive test

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 IN VITRO TEST: IN VIVO TEST:
 Floating lag time • Radiology
 Floating time • Scintigraphy
 Dissolution study • Gastroscopy
 Swelling index • Magnetic marker
 Mucoadhesive test monitoring

 Density • Ultrasonography

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 APPLICATIONS
 Enhanced bioavailability
 Sustained drug delivery
 Site specific drug delivery system
 Absorption enhancement
 Minimized adverse activity at the colon
 Reduced fluctuation of drug concentration

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MARKETED FORMULATIONS

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 CONCLUSION:
 FDDS promise to be potential approach for gastric retention.
 The goal of any drug delivery system is to provide a
therapeutic amount of drug to the proper site in the body and
also to achieve and maintain the desired plasma concentration
of the drug for a particular period of time.
 However, incomplete release of the drug, shorter residence
times of dosage forms in the upper GIT leads to lower oral
bio-availability.
 Such limitations of the conventional dosage forms have paved
way to an era of controlled and novel drug delivery system.
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 REFERNCE:
 Doshi S.M., Tank H.M., “Gastro Retention, An Innovation
over Conventional poorly Soluble Drugs: A Review”,
International Journal of Pharmaceutical and Chemical
Science, 2012;1(2):859-866.
 S.P. Vyas, Roop K. Khar, CONTROLLED DRUG
DELIVERY – Concepts & Advances, Vallabh Prakashan,
pp- 196-217.
 N.K. Jain, Progress in controlled & Novel Drug
Delivery System, 1st edition 2004 CBS Publishers, pp-
76-97. 38
 G. Chawla, P. Gupta, Pharmaceutical Technology, July
2003, 50-68

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