GASTRO RETENTIVE DRUG DELIVERY SYSTEM - ADVANTAGES, LIMITATIONS

AND DIFFERENT APPROACHES

Dr.K.Umasankar.,M.Pharm.,Ph.D.,FAGEKrishna Teja Pharmacy College

TirupathiEmail:- umasankar73@gmail.com

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CONTENTS

Introduction

Appropriate Candidate Drugs For GRDDS

Advantages

Limitations

Approaches

Conclusion

References

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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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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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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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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)

FS

HDS

A S

SS

CLASSIFICATIONCLASSIFICATION

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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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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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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 CO2 , 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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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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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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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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INTRA-GASTRIC FLOATING GASTROINTESTINAL DRUG DELIVERY SYSTEMSSystem 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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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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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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HOLLOW MICROSPHERES

Polymers used commonly: Polycarbonates, Cellulose acetate, Calcium alginate,

Eudragit S, agar and methoxylated pectin etc.

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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 -40oc 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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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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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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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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Marketed Products of GRDDSBrand name Delivery system Drug (dose) Company

nameValrelease® Floating capsule Diazepam (15mg) Hoffmann-LaRoche,

USA

Madopar® HBS(Prolopa® HBS)

Floating, CR capsule Benserazide (25mg) and L-dopa (100mg)

Roche Products, USA

Liquid Gaviscon® Effervescent Floating liquid alginate preparations

Al hydroxide (95 mg), MgCarbonate (358 mg)

GlaxoSmithkline,India

Topalkan® Floating liquid alginatePreparation

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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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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