This document provides an overview of gastroretentive drug delivery systems (GRDDS). It discusses appropriate candidate drugs, advantages and limitations of GRDDS. The document outlines various approaches to gastric retention including high density systems, floating systems, swelling systems, and mucoadhesive systems. Evaluation methods for GRDDS are also summarized, including in vitro tests to assess buoyancy, floating time, swelling, and dissolution behavior. The goal of GRDDS is to prolong gastric retention time of drugs and enable sustained release at the target site in the stomach.

1. GASTRO RETENTIVE DRUG DELIVERY
SYSTEM
PRESENT BY :- PATEL NISARG
(2nd semester M.pharm)
Department of Pharmaceutics
GUIDED BY :- DR. ANURADHA PATEL
1

2. CONTENTS
 INTRODUCTION
 APPROPRIATE CANDIDATE DRUGS FOR GRDDS
 ADVANTAGES & DISADVANTAGES
 LIMITATIONS
 FORMULATION
 FACTORS AFFECTING GASTRIC RETENTION TIME
 APPROACHES
 CONCLUSION
 REFERENCES
2

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.
• It is obtained by retaining dosage form into stomach and drug is being
released at controlled manner at specific site
3

4. APPROPRIATE CANDIDATE DRUGS
FOR GRDDS
 Drugs acting locally in the stomach.
 E.g. Antacids and drugs for H. Pylori viz., Misoprostol.
 Drugs that are primarily absorbed in the stomach.
 E.g. Amoxicillin
 Drugs that is poorly soluble at alkaline pH.
 E.g. Furosamide, Diazepam, Verapamil, etc.
 Drugs with a narrow absorption window.
 E.g. Cyclosporine, , Levodopa, Methotrexate etc.
 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 Helicobacter pylori.
4

5. ADVANTAGES OF GRDDS
 Enhanced bioavailability
 Sustained drug delivery/reduced frequency of
Dosing
 Targeted therapy for local action 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.
5

6. DISADVANTAGES OF GRDDS
 Floating systems has limitation, that they require high level of fluids in stomach for floating and
working efficiently. So more water intake is prescribed with such dosage form.
 In supine posture (like sleeping), floating dosage form may swept away (if not of larger size) by
contractile waves. So patient should not take floating dosage form just before going to bed.
 Food is also an important factor. Presence of food delays emptying time of food and dosage form.
So presence of food is preferable.
 Drugs having stability problem in high acidic environment, having very low solubility in acidic
environment and drugs causing irritation to gastric mucosa can not be incorporated into GRDDS.
 Bio/mucoadhesives systems have problem of high turn over rate of mucus layer, thick mucus layer &
soluble mucus related limitations.
 Swellable dosage form must be capable to swell fast before its exit from stomach & achieve size
larger than pylorus aperture. It must be capable to resist the housekeeper waves of Phase III of MMC.
6

7. 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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8. FORMULATION
 DRUG
 HPMC-K-100M
 SODIUM BICARBONATE
 CITRIC ACID
 TARTRIC ACID
 CROSS CARMELOSS SODIUM
 XANTHUM GUM
 MCC
 PVP-K-30
 MAGNESIUM STERATE
 TALC
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9. FACTORS AFFECTING GASTRIC RETENTION TIME
OF THE DOSAGE FORM
 Density: it is a function of dosage form buoyancy that is dependent on the density.
 Size: Dosage form units with a diameter of more than 7.5mm are reported to have an increased GRT
compared with those with a diameter of 9.9mm.
 Shape of dosage form: Tetrahedron and ring shaped devices with a flexural modulus of 48 and 22.5 kilo
pounds per square inch (KSI) are reported to have better GRT 90% to 100% retention at 24 hours
compared with other shapes.
 Nature of meal: Feeding of indigestible polymers or fatty acid salts can change the motility pattern of the
stomach to a fed state, thus decreasing the gastric emptying rate and prolonging drug release.
 Caloric content: GRT can be increased by 4 to 10 hours with a meal that is high in proteins and fats.
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10.  Gender: Mean ambulatory GRT in males (3.4±0.6 hours) is less compared with their age and
race matched female counterparts (4.6±1.2 hours), regardless of the weight, height and body
surface.
 Age: Elderly people, especially those over 70, have a significantly longer GRT.
 Posture: GRT can vary between supine and upright ambulatory states of the patient.
 Concomitant drug administration: Anticholinergics like atropine and propantheline, opiates
like codeine and prokinetic agents like metoclopramide and cisapride.
 Biological factors: Diabetes and Crohn’s disease.
10

11. APPROACHES TO GASTRIC RETENTION
• High-density systems. (HDS)
• Floating systems. (FS)
• Swelling and expanding systems. (SS)
• Mucoadhesive & Bioadhesive systems. (AS)
11

12. Classification
GRDDSAPPROACHES
HIGH DENSITY
SYSTEMS
FLOATING
SYSTEMS
HYDRODYNAMICAL
LY BALANCED
SYSTEMS HBS
GAS-GENERATING
SYSTEMS
VOLATILE LIQUID /
VACUUM CONTAINING
SYSTEMS
INTRAGATRIC FLOATING GASTROINTESTINAL
DRUG DELIVERY SYSTEM
INFLATABLE GASTROINTESTINAL DELIVERY
SYSTEMS
INTRAGASTRIC OSMOTICALLY CONTROLLED DRUG
DELIVERY SYSTEM
MATRIX TABLETS
RAFT-FORMING
SYSTEMS
HOLLOW
MICROSPHERES
ALGINATE BEADS
SUPER POROUS
HYDROGELS
EXPANDING
SYSTEMS
SWELLING
SYSTEMS
UNFOLDABLE
SYSTEMS
BIO/MUCOADHESIV
E SYSTEM
MAGNETIC
SYSTEMS
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13. 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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14. FLOATING DRUG DELIVERY
These have a bulk density lower than the gastric content. They remain float 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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15. 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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16. 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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17. 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.
17

18. 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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19. 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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20. MICRO POROUS RESERVOIR SYSTEM
 System can be float by flotation chamber, which may be vacuum or
filled with air or a harmless gas
 This device comprised of a drug reservoir encapsulated in microporous
compartment having pores on its surface.
 A floating chamber was attached at one surface which gives buoyancy to
entire device. Drug is slowly dissolves out via micro pores.
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21. RAFT FORMING
 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.
 This raft floats on gastric fluids because of a low density created by the formation of CO2.
Usually this contains a gel-forming agent and alkaline bicarbonates or carbonates
responsible for the formation of CO2 to make the system less dense to float on the gastric
fluids.
21

22. HOLLOW MICROSPHERES
 Hollow (porous) microsphere using polymers like polycarbonates have been prepared
using solvent evaporation technique. After preparation of microsphere, organic solvent
evaporates from it creating holes inside microsphere. A high (50%) drug loading can be
achieved.
 Polymers used commonly: Polycarbonates, Cellulose acetate, Calcium alginate, Eudragit S,
agar and methoxylated pectin etc.
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23. 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.
 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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SUPERPOROUS HYDROGELS

24. 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.
24
• Unfolding systems are systems which are
actually of larger size but they are folded to
decrease size and kept in capsules. In
stomach these systems comes out of
capsules and unfolds to larger size.
• The important factor for unfolding system is
shape memory. They should have sufficient
shape memory such that they retain their
unfolded (expanded) shape in stomach
against gastric motility and not get folded
again and escape out till the desired time
interval.

25. 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
25

26. 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.
26

27. EVALUATION
 A) IN-VITRO EVALUATION
 i) Floating systems
 a) Buoyancy Lag Time
 It is determined in order to assess the time taken by the dosage form to float on the
top of the dissolution medium, after it is placed in the medium. These parameters can
be measured as a part of the dissolution test.
 b) Floating Time
 Test for buoyancy is usually performed in SGF-Simulated Gastric Fluid maintained at
370C. The time for which the dosage form continuously floats on the dissolution media
is termed as floating time.
 c) Specific Gravity / Density
 Density can be determined by the displacement method using Benzene as displacement
medium.
27

28.  ii) Swelling systems
 a) Swelling Index
 After immersion of swelling dosage form into SGF at 370C, dosage form is
removed out at regular interval and dimensional changes are measured in
terms of increase in tablet thickness / diameter with time.
 b) Water Uptake
 It is an indirect measurement of swelling property of swellable matrix. Here
dosage form is removed out at regular interval and weight changes are
determined with respect to time. So it is also termed as Weight Gain.
 Tablet
 Water uptake = WU = (Wt – Wo) * 100 / Wo
 Where, Wt = weight of dosage form at time t
 Wo = initial weight of dosage form
 While we remove dosage form out and measure dimensions, the outer gel
layer is disturbed which can create a problem. So new idea came into picture
by which swelling index and water uptake can be measured without
tablet.
28

29.  B) IN-VITRO DISSOLUTION TESTS
 A. In vitro dissolution test is generally done by using USP apparatus with paddle and GRDDS is
placed normally as for other conventional tablets. But sometimes as the vessel is large and
paddles are at bottom, there is much lesser paddle force acts on floating dosage form which
generally floats on surface. As floating dosage form not rotates may not give proper result
also not reproducible results. Similar problem occur with swellable dosage form, as they are
hydrogel may stick to surface of vessel or paddle and gives irreproducible results.
 In order to prevent such problems, various types of modification in dissolution assembly made
are as follows.
 B. To prevent sticking at vessel or paddle and to improve movement of dosage form, method
suggested is to keep paddle at surface and not too deep inside dissolution medium.
 C. Floating unit can be made fully submerged, by attaching some small, loose, non- reacting
material, such as few turns of wire helix, around dosage form. However this method can inhibit
three dimensional swelling of some dosage form and also affects drug release.
 D. Other modification is to make floating unit fully submerged under ring or mesh assembly
and paddle is just over ring that gives better force for movement of unit.
 E. Other method suggests placing dosage form between 2 ring/meshes.
29

30. 30

31.  F. In previous methods unit have very small area, which can inhibit 3D swelling
of swellable units, another method suggest the change in dissolution vessel that
is indented at some above place from bottom and mesh is place on indented
protrusions, this gives more area for dosage form.
 G. Inspite of the various modifications done to get the reproducible results,
none of them showed co-relation with the in-vivo conditions. So a novel
dissolution test apparatus with modification of Rossett-Rice test Apparatus was
proposed.
 Rossett-Rice test is used for predicting in-vitro evaluation of directly acting
antacid (action by chemical neutralization of acid), where HCl is added
to mimic the secretion rate of acid from the stomach.
 In this modified apparatus as shown in figure, it has side arm from bottom of
beaker such that it maintains volume of 70ml in beaker and fresh SGF is added
from burette at 2 ml/min rate. Thus sink condition is maintained
 along with easy sampling. Stirring is done by magnetic stirrer at 70-75 RPM.
 Thus this apparatus mimics in-vivo condition for GRDDS.
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32.  C) IN-VIVO EVALUATION
 a) Radiology
 X-ray is widely used for examination of internal body systems.. Barium Sulphate is widely used Radio Opaque
So, BaSO4 is incorporated inside dosage form and X-ray images are taken at various intervals to view GR.
 b) -Scintilography
 Similar to X-ray, -emitting materials are incorporated into dosage form and then images are taken by scintigraphy.
Widely used -emitting material is 99Tc.
 c) Gastroscopy
 Gastroscopy is peroral endoscopy used with fiber optics or video systems. Gastroscopy is used to inspect visually
effect of prolongation in stomach. It can also give the detailed evaluation of GRDDS.
 d) Magnetic Marker Monitoring
 In this technique, dosage form is magnetically marked with incorporating iron powder inside, and images can be
taken by very sensitive bio-magnetic measurement equipment. Advantage of this method is that it is radiation less
and so not hazardous.
 e) Ultrasonography
 Used sometimes, not used generally because it is not traceable at intestine.
 f) 13C Octanoic Acid Breath Test
 13C Octanoic acid is incorporated into GRDDS. In stomach due to chemical reaction, octanoic acid liberates CO2
which comes out in breath. The important Carbon atom which will come in CO2 is replaced with 13C isotope. So
upto which 13CO2 gas is observed in breath can be considered as gastric retention time of dosage form. As the
dosage form moves to intestine, there is no reaction and no CO2 release. So this method is cheaper than other.
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33. 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
33

34. Marketed Products of GRDDS
Brand name Delivery system Drug (dose) Company
name
Valrelease® 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), 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
34

35. OTHE APPROCHES FOR FLOATING
SYSTEMS
 CLASSIFICATION OF THE FLOATING SYSTEMS:
 i) Non-effervescent systems
 Single unit
 Multiple units
 ii) Effervescent systems
 Single unit
 Multiple units
35

36. NON EFFERVESENT
 SINGLE UNIT SYSTEMS
 a) Floating tablet
 It’s a matrix tablet with single layered or bi-layered.
 Matrix tablet were prepared by incorporating gel forming hydrocolloids like
HPMC, which the most commonly used polymer for floating. Out of various
grades of HPMC, low viscosity grade are use for floating purpose. Mixture of
alginate and HPMC also prepared for floating tablet.
 BILAYER CAPSULE
 Capsule is filled with non compressed bilayer formulation. One layer is drug
releasing layer and other is floating layer. Both the layer consists of
hydrocolloid gelling layer such as HPMC, gums, polysaccharides and gelatin
36

37. MULTIPLE UNIT
 ALGINATE BEADS WITH AIR COMPARTMENT
 These are also calcium alginate beads but the
difference is that the calcium alginate core is
separated by air compartment from a coating
membrane calcium alginate or mixture of calcium
alginate and PVA.
 During the preparation of calcium alginate beads
before drying process the beads are coated with the
coating solution which may be calcium alginate or
mixture of calcium alginate and PVA, and then they
are dried.
37

38. OIL ENTRAPPED GEL BEADS
Vegetable oil is use as floating carrier as they are light weight
and hydrophobic used for floating by incorporating it into gel
matrix of beads. Oil entrapped beads are prepared by both
calcium alginate bead and calcium pectinate beads.
Pectin has some emulsification property, so aqueous solution
of pectin is mix edible oil. Emulsion is obtained by
homogenization. And this emulsion is extruded into calcium
chloride solution to form beads which are separated, washed
and dried.
38

39. MICROBALLOON
 Microballoons are the hollow microspheres which are
completely hollow from inside forming cavity inside and
drug loaded in their outer shells are prepared by an
emulsion solvent diffusion method. Organic phase of drug
and polymer in ethanol/dichloromethane is poured on to
aqueous solution of PVA maintained at 40oC. So gas
phase of organic solvent is generated in dispersed
polymer droplet, goes out by creating internal cavity
which is responsible for floating
39

40. Floating powder
 Floating powder which can be filled in capsule or compress to tablet was
made up of drug, pH dependent polymer - which was a water soluble
salt of alginic acid (such as a sodium or potassium alginate) and a pH
independent hydrocolloid gelling agent (such as HPMC, HPC, MC) and
binder.
40

41. QUESTIONS….
 WHAT IS GRDDS ? HOW IT CAN BE ACHIVED ? WRITE A NOTE ON FDDS?
 ADVANTAGES OF GRDDS?
 FORMULATION OF FLOATING MICROSPHERE?
 EXPLAIN HIGH DENSITY APPROCH?
 DESCRIBE EFFERVESENT BASED FLOATING DRUG DELIVARY SYSTEM. IN-VITRO
EVALUATION OF GRDDS?
 DESCRIBE CONCEPT OF GRDDS. MENTION DIFFERENT APPROCHES TO GET
GESTRORETNTION AND DESCRIBE ANY ONE APPROCH.
 DISCUSS THE CONCEPT OF IN-VITRO DISSOLUTION.STUDY FOR FLOATING DRUG
DELIVARY SYSTEM.
 ENUMERATE ON NON-EFFERVESENT TYPE OF SINGLE & MULTIPLE FLOATING
GDDS.
 DESCRIBE FORMULATION ASPECTS ,EXCIPIENTS USED IN MFG & EVALUTION
PARAMETER OF EFFERVESENT ANTACID GRANULES.
 VARIOUS MECHANISM FOR FLOATING FORMULATION.
41

42. 42