NDDS TOPICS BY PROF. SHASHANK CHAURASIYA

1. Gastro Retentive
Drug Delivery
System
Prof. Shashank Chaurasiya
Asst. Professor
Bansal College of Pharmacy, Bhopal

2. CONTENTS
2
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

3. 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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5. GASTROINTESTINALTRACT
PHYSIOLOGY
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Migrating myoelectric cycle
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7. POTENTIAL CANDIDATESFOR
GRDDS
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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.

8. 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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9. DRUG CANDIDATES NOT
SUITABLE FOR GRDDS
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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.

10. FACTORS AFFECTING THE GRDDS
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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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13. 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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14. DEMERITS
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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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17. 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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19. 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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20. 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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21. TYPES OF FLOATING SYSTEM
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22.  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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26.  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 drug with
gelforming hydrocolloids.
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27. 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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28. 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, forming a continuous layer called raft.
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29. 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 drug.
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30. 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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31. MICROSPHERES
loaded with drugs
solvent diffusion/
Microballons/ hollow microspheres
prepared by solvent evaporation or
evaportaion methods.
Buoyancy and drugs release depends on quality of
polymers, plasticizer polymer and solvents used.
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32. 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.
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33. B. HIGH DENSITY SYSTEM
Gastric contents have a density close to water.
A density close to 2.5g/cm3 is necessaryfor
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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34. C. BIOADHESIVE OR
MUCOADHESIVE SYSTEM
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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:

35. 1. The wetting theory.
2. The diffusion theory.
3. The absorption theory.
4. The electron theory.
POLYMER
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MUCUS
MEMBRANE

36. 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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37. 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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38. 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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39. 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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40. METHODOLOGY
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Direct compression method
Melt granulation technique
Effervescent technique
Spray drying technique
Solvent evaporation technique
Wet granulation technique
Ionotropic gelation technique

41. EVALUATION PARAMETERS
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Pre- compression test:
• Size and shape
• Particle size
• Density
• Specific gravity
• Flow properties
Post compression test:
• Thickness and diameter
• Hardness and friability
• Weight variation test
• floating time
• Content uniformity
• Dissolution test
• Mucoadhesive test

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

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

44. MARKETED FORMULATIONS
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45. 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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