Gastro-retentive Drug Delivery System (GRDS)

• Oral route is most acceptable route for drug administration. Apart

from conventional dosage forms several other forms were developed
in order to enhance the drug delivery for prolonged time period and
for delivering drug to a particular target site.

• Oral administration have some limitation in terms of bioavailability

due to

 Some drugs with Narrow absorption window and drugs

which undergo carrier mediated transport in the region of stomach and
upper part of small intestine have poor bioavailability
 Poor GIT residence time
 Unpredictable Gastric emptying rate

• In order to overcome such issues, gastro retentive drug delivery

systems were developed.
Absorption window and Bioavailability
 DEFINITION
• These are the drug delivery systems which possess the ability of
retaining the drug in the GIT particularly in the stomach for
prolonged period of time.
• After the retention drug release for prolong period of time with
broad absorption window assure for it maximum bioavailability
without causing any gastric disturbances.
 In Fed state – ingestion of meals pattern of MMC cycle similar , contraction
reduces the size of meals by action of pylorus or motility
It last for 0- 5 min
 GIT tract Transit or residence time
Fluid Solid
Stomach 50 min 8 hrs.
Small intestine 2-6 hrs. 4-9 hrs.
Large intestine 2-6 hrs. 3 hrs. to 3 days
NEED FOR GASTRORETENTIVE DRUG DELIVERY SYSTEM

Enhance Bioavailability and Therapeutics effect : A controlled drug delivery system with
prolonged residence time in the stomach

Drugs which are locally targeting in the stomach : (MISOPROSTOL, ANTACIDS ,

ANTIBIOTICS AGAINST H.PYLORI).

Have an absorption window in stomach or in the upper small intestine (L-DOPA, P-

AMINOBENZOIC ACID, FUROSEMIDE, AMOXICILLIN, METRONIDAZOLE, METHOTREXATE).

Are unstable in the intestine or colonic environment :(CAPTOPRIL).

Exhibit low solubility : (DIAZEPAM, VERAPAMIL).

Drug unstable in GIT : Antibiotics like penicillin , hormone , peptides

Absorbed by transporter mechanism (PACLITAXEL).

 ADVANTAGES
•Improved drug absorption, because of increased GRT and more time spent by the
dosage form at its absorption site.

•Enhance Solubility & Bioavailability: long term retention of drug in GIT improve
solubility of drug leads to faster absorption & more bioavailability of drugs achieved

•Effective delivery of drug with narrow absorption window: L-DOPA,

Furosemide, Riboflavin , PABA etc

•Prolong duration of action : controlled delivery of drugs

•Delivery of drugs for local action in the stomach: Antacids , Antibiotics

•Minimizing mucosal irritation by drugs, by drug releasing slowly at a controlled rate.

•Treatment of gastrointestinal disorders( Drug targeting) such as gastro-esophageal

reflux: IBD, Ulcerative colitis , Crohns disease etc

•Ease of administration, convenient and better patient compliance.

ADVANTAGES
ADVANTAGES
ADVANTAGES
ADVANTAGES
 LIMITATIONS
 They require a sufficiently high level of fluids in the stomach for
the drug delivery buoyancy, to float therein and to work
efficiently.

 Floating systems are not feasible for those drugs that have
solubility or stability problems in gastric fluid.

 Drugs which are well absorbed along the entire GI tract and
which undergoes significant first- pass metabolism, may not
be desirable candidates for GRDDS since the slow gastric
emptying may lead to reduced systemic bioavailability.

 Drugs that are irritant to gastric mucosa are not suitable for
GRDDS.
o Fed & Unfed state:
Unfed state – The motility of GIT is more due to MMC event hence if FDDS rapidly moves
from stomach to intestine ( more gastric emptying rate )
Fed state – MMC cycle delayed hence Gastric Residence Time (GRT) of FDDS is
enhanced & more drug get bioavailable

o Nature of Meal: Fatty foods delayed the gastric emptying rate hence GRT increases

o Biological factor :
Age : Elder (more than 70 years) significantly longer the GRT of system than adult
Gender : Average GRT for Female – 4.6 hrs & for male – 3.4 hrs
Posture : Lying posture affect on GRT
Disease state : Diabetics , Crohn's disease :
CLASSIFICATION HYDRODYNAMICALLY
BALANCED SYSTEMS HBS

INTRAGATRIC FLOATING
GAS-GENERATING SYSTEMS GASTROINTESTINAL DRUG
DELIVERY SYSTEM
HIGH DENSITY SYSTEMS
INFLATABLE
VOLATILE LIQUID / VACUUM
GASTROINTESTINAL DELIVERY
CONTAINING SYSTEMS
SYSTEMS
FLOATING SYSTEMS
INTRAGASTRIC OSMOTICALLY
RAFT-FORMING SYSTEMS CONTROLLED DRUG DELIVERY
SYSTEM
SUPER POROUS HYDROGELS

HOLLOW MICROSPHERES
GRDDS APPROACHES

ALGINATE BEADS

SWELLING SYSTEMS

EXPANDING SYSTEMS

UNFOLDABLE SYSTEMS

BIO/MUCOADHESIVE SYSTEM

MAGNETIC SYSTEMS
Iron oxide, zinc oxide , BaSo4

Drug or API
LIMITATIONS OF FLOATING SYSTEMS
Requires sufficient high level of fluids in the stomach for the
drug delivery to float.
Floating system is not feasible for those drugs that have
solubility or stability problem in gastric fluids.
The dosage form should be administered with a minimum of
glass full of water (200-250 ml).
The drugs, which are absorbed throughout gastro-intestinal
tract, which under go first-pass metabolism (nifedipine,
propranolol etc.), are not desirable candidate.
Some drugs present in the floating system causes irritation to
gastric mucosa.
 Floating Techniques

– Effervescent
• Volatile liquid containing systems
• Gas generating systems
– Non-Effervescent
• Colloidal gel barrier systems
• Alginate beads
• Hollow Microspheres
• Microporous Compartment System
Citric acid + NaOH + drug = Sodium citrate + CO2 (effervescent)
Mechanism of effervescent & drug release :
 Volatile liquid containing systems
• Incorporates an inflatable chamber, which contains a
liquid e.g. ether, cyclopentane, that gasifies at body
temperature to cause the inflatation of the chamber
in the stomach.
• The device may also consist of a bioerodible plug
made up of PVA, Polyethylene, etc. that gradually
dissolves causing the inflatable chamber to release gas
and collapse after a predetermined time to permit the
spontaneous ejection of the inflatable systems from
the stomach.
• There systems are very less used as the gas
generating systems are more safe.
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.
 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.
 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.
 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.

51
General tests:
Appearance, hardness, friability, Drug content, weight variation,
Uniformity of content, Dissolution time and drug release.

Buoyancy(Floating) lag time :

the buoyancy lag time and duration of buoyancy were performed
in the USP dissolution apparatus II in simulated gastric fluids
(SGF) and 0.1N HCl maintained at 370C environment. The time
interval between the introduction of the tablet into the dissolution
medium and till the tablet reaches the surface was taken as
buoyancy lag time and the duration of buoyancy was observed
visually.
 Floating lag time

 Time required for the tablet to reach on surface of

fluid called floating lag time
 Success of GRDS depends on floating lag time , it
should be less so tablet can easy to float on GIT fluid
for prolong duration of time
(Total Floating Time)

Total Floating Time

(Swelling Index)
Initial
Weight of
Tablet

Final
Weight of
Tablet
CONCLUSION

The development of GRDDs can be

advantageous for the
administration of some important
drugs and significantly improves
their therapeutic outcome.

Gastroretentivity of a DF can be achieved

by the development of devices that can
be significantly expand their volume by
unfolding or swelling, adhering to gastric
mucosa, or have the suitable density to
sink or float over the gastric fluids.