This is about novel drug delivery system that is GRDDS

1. Gastro-Retentive Drug Delivery
System
PRESENTED BY
Rajshri Rokade
F.Y.M-PHARMACY
Department of
Pharmaceutics
Under guidance of
Dr. Nalanda Borkar
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2. Sr.No. Index Page
No.
1 What is GRDDS? 3
2 Need and Requirement for GRDDS 4
3 Physiology of the Stomach 8
4 Approches to Gastric Retention 9
5 Advantages of GRDDS 19
6 In-Vivo Evaluation 20
7 Marketed products of GRDDS 21
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3. WHAT IS GRDDS???
Gastroretentive drug delivery is an approach to
prolong gastric residence time, thereby targeting
site-specific drug release in the upper
gastrointestinal tract (GIT) for local or systemic
effects.
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4. NEED FOR GRDDS…???
Oral drug delivery system Sustained drug delivery systems
These drug delivery systems suffer from mainly two adversities:
short gastric retention time(GRT) and
unpredictable short gastric emptying time (GET)
which can result in incomplete drug release from the dosage form in the absorption zone
(stomach or upper part of small intestine) leading to diminished efficacy of administered
dose.
To formulate a site-specific orally administered controlled release dosage form, it is
desirable to achieve a prolong gastric residence time by the drug delivery. Prolonged gastric
retention time (GRT) in the stomach could be advantageous for local action e.g. treatment of
peptic ulcer, etc.
4

5. POTENTIAL DRUG CANDIDATES FOR
GASTRORETENTIVE DRUG DELIVERY
SYSTEMS
1. Drugs acting locally in the stomach(active in stomach)
e.g. Antacids and drugs for H. Pylori viz., Misoprostol
2. Drugs that are primarily absorbed in the stomach
e.g. Amoxicillin
3. Drugs that are poorly soluble at alkaline pH
e.g. Furosemide, Diazepam, Verapamil, etc.
4. Drugs with a narrow window of absorption
e.g. Cyclosporine, Methotrexate, Levodopa, etc.
5. Drugs which are absorbed rapidly from the GI tract.
e.g. Metronidazole, tetracycline.
6. Drugs that degrade in the colon.
e.g. Ranitidine, Metformin HCl.
7. Drugs that disturb normal colonic microbes
e.g. antibiotics against Helicobacter pylori.
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6. DRUGS UNSUITABLE FOR GRDDS
1] Drugs that have very limited acid solubility
phenytoin etc.
2) Drugs that suffer instability in the gastric environment e.g.
erythromycin etc.
3) Drugs intended for selective release in the colon
5-amino salicylic acid and corticosteroids
etc.
Factors affecting the gastroretentive system.
1. DENSITY.
2. SIZE.
3. SHAPE OF DOSAGE FORM.
4. SINGLE OR MULTIPLE UNIT FORMULATION.
5. FED OR UNFED STATE. 6

7. 7. NATURE OF MEAL 8. FREQUENCY OF FEED 9. GENDER. 10. AGE.
11. POSTURE. 12.CONCOMITANT DRUG. 13. BIOLOGICAL FACTORS.
Requirements For Gastric Retention
The dosage form must satisfy certain requirements:
Able to withstand the forces caused by peristaltic
waves in the stomach and the constant contractions
and grinding and churning mechanisms.
Resist premature gastric emptying.
Device should be removed from the stomach with
ease
7

8. Physiology Of The Stomach
The stomach is an organ with a capacity for storage and mixing.
The antrum region is responsible for the mixing and grinding of
gastric contents.
Under fasting conditions, the stomach is a collapsed bag with a
residual volume of approximately 50ml and contains a small
amount of gastric fluid (pH 1–3) and air.
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9. APPROACHES TO GASTRIC RETENTION
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10. 10

11. Floating drug delivery systems
The major requirements for floating drug delivery system are:
• Release contents slowly to serve as a
reservoir.
• Maintain specific gravity lower than gastric contents
(1.004 – 1.01 gm/cm3).
• Form a cohesive gel barrier.
The inherent low density can be provided by the
entrapment of air (e.g. hollow chambers) or by the incorporation
of low density materials (e.g. fatty materials or oils, or foam
powder.
Multiple-unit floating system preferred over Single-unit dosage
because of dose dumping.
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12. Multiple-unit floating system:
Air compartment multiple-unit system hollow microspheres
(microballoons)
Microparticles.
Based on the mechanism of buoyancy two distinctly different technologies,
i.e. non-effervescent and effervescent systems have been utilized in the
development of floating drug delivery system.
Non-effervescent Systems
Prepared from gel-forming or highly swellable cellulose type hydrocolloids,
polysaccharides or matrix forming polymers like polyacrylate, polycarbonate,
polystyrene and polymethacrylate. 12

13. The air trapped by the swollen polymer confers buoyancy to these dosage forms.
Excipients used are HPMC, polyacrylates, polyvinyl acetate, carbopol, agar, sodium alginate,
calcium chloride, polyethylene oxide and polycarbonates.
DRUG + GEL- FORMING HYDROCOLLOID= BUOYANT
Single-unit dosage for contains one or more gel-forming hydrophilic polymers.
Excipients:
 HEC
 HPMC
 NaCMC
 Polycarbophil,
 Polyacrylate, Polystyrene,
 agar, carrageenans or alginic acid.
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14. Microballoons / Hollow microspheres
 Microballoons / Hollow microspheres loaded with drugs prepared by solvent
evaporation or solvent diffusion / evaporation methods.
 Polymers used polycarbonate, cellulose acetate, calcium alginate, agar, and low
methoxylated pectin etc. Buoyancy and drug release depends on quantity of polymers,
plasticizer polymer and solvents used.
 The microballoons floated continuously over the surface of an acidic dissolution media
containing surfactant for >12 hours.
 Are the best because they combine the advantages of multiple-unit system and good
floating.
14

15. Microporous compartment systems
Based on the principle of the encapsulation of a drug reservoir inside a
microporous compartment with pores along its top and bottom walls.
Gastric fluid enters through the aperture, dissolves the drug and causes the
dissolved drug for continuous transport across the intestine for drug absorption.
EFFEREVESENT GAS GENERATIONG
SYSTEM
Floatability can be achieved by generation of gas bubbles(Carbon dioxide) These
buoyant systems utilize matrices prepared with swellable polymers such as
polysaccharides (e.g. chitosan), effervescent components (e.g. sodium bicarbonate,
citric acid or tartaric acid, sodium alginate and sodium bicarbonate.
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16. Multiple unit floating dosage forms generate gas (carbon dioxide) when ingested,
floating mini capsules with a core of sodium bicarbonate, lactose and polyvinyl
pyrrolidone (PVP) coated with hydroxypropyl methylcellulose (HPMC), and
floating system based on ion exchange resin technology etc.
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17. BIOADHESIVE OR MUCOADHESIVE SYSTEMS
Delivery device within the human to enhance drug absorption in a site-specific
manner.
 bio adhesive polymers used which adhere to the epithelial surface in the
stomach & improves the prolongation of gastric retention.
 These mechanisms are:
1) The wetting theory 2) The diffusion theory
3) The absorption theory 4) The electron theory
Materials commonly used for bioadhesion are poly
acrylic acid, chitosan, cholestyramine, sodium
alginate, hydroxypropyl methylcellulose (HPMC),
sucralfate, tragacanth, dextrin, polyethylene glycol and polylactic acids etc.
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18. Super porous hydrogels
In this approach to improve gastric
retention time (GRT) super porous
hydrogels of average pore size >100
micro meter, swell to equilibrium size
within a minute due to rapid water uptake
by capillary wetting through numerous
interconnected open pores. They swell to
a large size and are intended to have
sufficient mechanical strength to
withstand pressure by gastric contraction.
MAGNETIC SYSTEMS
Enhances the gastric retention
time (GRT) 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.
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19. Advantages of Gastroretentive Drug Delivery System
 Improves patient compliance e.g. Furosemide
 Enhanced bioavailability.
 Increased Gastric retention time.
 Enhanced absorption of drugs which solubilise only in stomach.
 Drug releases in controlled manner for prolonged period e.g. b-lactams.
 Site-specific drug delivery to stomach can be achieved.
 Superior to single unit floating dosage -- no risk of dose dumping.
 Avoids gastric irritation.
 Better therapeutic effect of short half-life drugs can be achieved.
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20. IN-VIVO EVALUATION
a) Radiology
b) Scintigraphy
c) Gastroscopy
d) Magnetic Marker Monitoring
e) Ultrasonography
f) 13C Octanoic Acid Breath Test
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21. Commonly used drugs in formulation of
gastroretentive dosages forms
 Floating tablets
 Floating capsules
 Floating microspheres
 Floating granules
 Powders
 Films
 Acetaminophen, Acetylsalicylic acid,
 Ampicillin, Amoxicillin trihydrate,
 Atenolol, Captopril.
 Chlorpheniramine maleate, Cipro.
 Diltiazem, Fluorouracil, Isosorbide
dinitrate and mononitrate,
 PABA, Prednisolone,
 Theophylline, Verapamil
 Diazepam,
 Furosemide, L-DOPA
 Nicardipine, Misoprostol, Propranolol,
 Aspirin, Griseofulvin, p-nitro aniline,
 Ibuprofen, Terfenadine
 Diclofenac sodium, Indomethacin,
 Prednisolone
 Several basic drugs
 Cinnerzine
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22. Gastroretentive products available in
the market
Brand Name
Cifran OD ®
Madopar ®
Valrelease ®
Topalkan ®
Almagate FlatCoat ®
Liquid Gavison ®
Conviron
Cytotec®
Active Ingredient(s)
Ciprofloxacin
L-DOPA and Benserazide
Diazepam
Aluminium-magnesium antacid
Aluminium-magnesium antacid
Aluminium hydroxide,
Ferrous sulphate
Misoprostol 22

23. References:
http://www.pharmainfo.net/reviews/gastroretentive-drug-
delivery-system-overview
http://www.pharmainfo.net/reviews/gastroretentive-drug-
delivery-system-overview
http://www.touchbriefings.com/pdf/17/pt031_p_garg.pdf
http://iglobaljournal.com/wp-content/uploads/2011/12/4.-
Santosh-Shep-et-al.pdf
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