Gastrorentive drug delivery systems

1. GASTRO RETENTIVE DRUG DELIVERY
SYSTEM - ADVANTAGES, LIMITATIONS AND
DIFFERENT APPROACHES
Dr.K.Umasankar.,M.Pharm.,Ph.D.,FAGE
Krishna Teja Pharmacy College
Tirupathi
Email:- [email protected]
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2. CONTENTS
Introduction
Appropriate Candidate Drugs For GRDDS
Advantages
Limitations
Approaches
Conclusion
References
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3. INTRODUCTION
•Oral Drug Delivery is widely used in pharmaceutical field to treat the diseases.
•Some drugs are absorbed at specific site only these require release at that
specific site.
•Gastro Retentive Drug Delivery(GRDDS) is one of the site specific drug
delivery for the delivery of the drugs at stomach.
•Retaining the Dosage Form in stomach and drug is being released at
controlled manner at specific site
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4. APPROPRIATE CANDIDATE DRUGS FOR GRDDS
•Drugs - acting locally in the stomach.
E.g. Antacids and drugs for H. Pylori viz., Misoprostol.
•Drugs - primarily absorbed in the stomach.
E.g. Amoxicillin
•Drugs - poorly soluble at alkaline pH.
E.g. Furosamide, Diazepam, Verapamil, etc.
•Drugs - with a narrow absorption window.
E.g. Cyclosporine, , Levodopa, Methotrexate etc.
• Drugs - 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 Helicobacter pylori.
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5. ADVANTAGES
Enhanced bioavailability
Sustained drug delivery/reduced frequency
of Dosing
Targeted therapy for local ailments in the
upper GIT
Reduced fluctuations of drug concentration
Improved selectivity in receptor activation
Reduced counter-activity of the body
Extended effective concentration.
Minimized adverse activity at the colon.
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6. LIMITATIONS
The drug substances that are unstable in the acidic environment of the
stomach are not suitable candidates to be incorporated in the systems.
These systems require a high level of fluid in the stomach for drug delivery to
float and work efficiently.
Not suitable for drugs that have solubility or stability problem in GIT.
Drugs which are irritant to gastric mucosa are also not suitable
These systems do not offer significant advantages over the conventional dosage
forms for drugs, which are absorbed throughout GIT.
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APPROACHES FOR PROLONGING THE
GASTRIC RESIDENCE TIME
•High-density systems. (HDS)
•Floating systems. (FS)
•Swelling and expanding
systems. (SS)
•Mucoadhesive & Bioadhesive
systems. (AS)
F
S
HDS
A S
S
S

8. CLASSIFICATIONCLASSIFICATION
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9. HIGH DENSITY SYSTEM
•Gastric contents have a density close to water (1.004 g cm
−3
). When
the patient take high-density pellets, they sink to the bottom of the
stomach where they become entrapped in the folds of the antrum
and withstand the peristaltic waves of the stomach wall.
•A density close to 2.5 g cm
−3
seems necessary for significant
prolongation of gastric residence time.
•Barium sulphate, zinc oxide, iron powder, and titanium dioxide
are examples for excipients used.
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10. FLOATING DRUG DELIVERY
These have a bulk density lower than the gastric content. They remain buoyant in the
stomach for a prolonged period of time, with the potential for continuous release of drug.
They Include:
Hydrodynamically balanced systems (HBS)
Gas-generating systems
Volatile liquid/ vacuum containing systems
Raft-forming systems
Low-density systems
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11. GAS GENERATING SYSTEMS
•Carbonates or bicarbonates, which react with
gastric acid or any other acid (e.g., citric or
tartaric) present in the formulation to produce
CO
2
, are usually incorporated in the dosage
form, thus reducing the density of the system
and making it float on the media.
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12. MATRIX TABLETS
Single layer matrix tablet is prepared by
incorporating bicarbonates in matrix forming
hydrocolloid gelling agent like HPMC, Chitosin,
Alginate or other polymers and drug.
Bilayer tablet can also be prepared by gas
generating matrix in one layer and second layer
with drug for its SR effect.
Triple layer tablet also prepared having first
swellable floating layer with bicarbonates, second
sustained release layer of drug and third rapid
dissolving layer of bismuth salt.
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13. INFLATABLE GASTROINTESTINAL DELIVERY

•System is incorporated with an inflatable
chamber which contains liquid ether - gasifies
at body temperature to cause the chamber to
inflate in stomach.
•Inflatable chamber is loaded with a drug
reservoir which can be a drug, impregnated
polymeric then encapsulated
in a gelatin capsule.
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14. INTRAGASTRIC OSMOTICALLY CONTROLLED DDS
Comprised of both an osmotic pressure controlled drug delivery device and an
inflatable floating support in a biodegradable capsule.
In stomach, the capsule quickly disintegrates and release the intragastric
osmotically controlled drug delivery device.
Inflatable support forms a deformable hollow polymeric bag containing liquid
that gasifies at body temperature to inflate the bag.
Consists of 2 compartments:
•Drug reservoir
•Osmotically active compartment.
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15. INTRA-GASTRIC FLOATING
GASTROINTESTINAL DRUG DELIVERY
SYSTEMS
System can be float by flotation chamber, which may be vacuum or
filled with air or a harmless gas
Drug reservoir is
encapsulated inside
a microporous
compartment
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16. HYDRODYNAMICALLY BALANCED SYSYTEMS
Prepared by incorporating a high level (20-75%w/w) gel-forming
hydrocolloids. e.g.:- Hydoxyethylcellulose, hydroxypropylcellulose,
HPMC & Sod. CMC into the formulation and then compressing these
granules into a tablets or capsules.
 It maintains the bulk density less than 1.
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17. 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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18. HOLLOW MICROSPHERES
Polymers used commonly: Polycarbonates, Cellulose acetate, Calcium alginate,
Eudragit S, agar and methoxylated pectin etc.
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19. ALGINATE BEADS
•Prepared by dropping
sodium alginate
solution into aqueous
solution of calcium
chloride, causing the
precipitation of calcium
alginate
•Freeze dry in liquid
nitrogen at -40
o
c for
24h.
•Beads-spherical and
2.5 mm in diameter.
SUPERPOROUS HYDROGELS
Swellable agents have pore
size ranging between 10nm
to 10µm.
Superporous hydrogels will
swell more than the swelling
ratio 100,
This is achieved by co-
formulation of a hydrophilic
particulate material, and Ac-
Di-Sol (crosscarmellose).
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20. EXPANDABLE SYSTEMS
1.UNFOLDED SYSTEMS
2.SWELLABLE SYSTEMS
The swelling is usually results
from osmotic absorption of
water.
The device gradually
decreases in volume and
rigidity as a result depletion of
drug and expanding agent
and/or bioerosion of polymer
layer, enabling its elimination.
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21. MUCOADHESIVE SYSTEMS
•The basis of mucoadhesion is that a dosage form can stick
to the mucosal surface by different mechanisms.
•Examples for Materials commonly used for bioadhesion are
poly (acrylic acid) (Carbopol®, polycarbophil), chitosin,
Gantrez® (Polymethyl vinyl ether/maleic anhydride
copolymers), cholestyramine, tragacanth, sodium alginate
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22. MAGNETIC SYSTEM
Based upon the principle that dosage form contains
a small internal magnet, and a magnet placed on the
abdomen over the position of stomach can enhance
the GRT.
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23. Marketed Products of GRDDS
Brand nameDelivery systemDrug (dose) Company
name
Valrelease® Floating capsule Diazepam (15mg) Hoffmann-LaRoche,
USA
Madopar® HBS
(Prolopa® HBS)
Floating, CR capsuleBenserazide (25mg) and L-
dopa (100mg)
Roche Products,
USA
Liquid Gaviscon®Effervescent Floating
liquid alginate
preparations
Al hydroxide (95 mg), Mg
Carbonate (358 mg)
GlaxoSmithkline,
India
Topalkan® Floating liquid alginate
Preparation
Al – Mg antacid Pierre Fabre Drug,
France
Conviron® Colloidal gel forming
FDDS
Ferrous sulphate Ranbaxy, India
Cytotech® Bilayer floating capsule Misoprostol (100μg/200μg)Pharmacia, USA
Cifran OD® Gas-generating floating
form
Ciprofloxacin (1gm) Ranbaxy, India
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24. CONCLUSION
•Gastro retentive drug delivery systems have
emerged as a current approach of controlled
delivery of drugs that exhibit an absorption window.
•All these drug delivery systems have their own
advantages and drawbacks.
•To design a successful GRDDS, it is necessary to
take into consideration the physicochemical
properties of the drug, physiological events in the
GIT, formulation strategies, and correct combination
of drug and excipients.
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