 Gastroretentive drug delivery isan

approach to prolong gastric residence

time, thereby targeting site-
specific drug release in the upper
gastrointestinal tract (GIT) for local
or systemic ef ects.
 Anatomically the stomach is
divided into 3 regions:

 Fundus
 Body and
 pylorus
 Phase I is basal phase, which is silent period of 30-60
minutes and characterized by lack of secretory,
electrical and contractile activity and there is no
contractions.

 Phase II is pre-burst phase, which exhibit intermittent

action for 20-40 minutes. Some bile secretion started and
contractile motions increases frequency. Mucus
discharge is started during later part of phase II.

 Phase III is burst phase, which is characterized by

intense and large regular contractions termed as “house
keeper waves”. These waves sweep off undigested food
by maximizing the pyloric opening and lasts for 10-20
minutes.Thus, these phase enables efficient evacuation of
the stomach contents.

 Phase IV is transition period up to 5 minute, between

phase III & I.
 Improved drug absorption.
 Enhanced bioavailability.
 Reduced dose frequency.
 Controlled drug delivery of drug
 Site specific drug delivery.
 Drugs acting localy in the stomach(activein
stomach)
e.g. Antacidsand drugs for H. Pylori viz., Misoprostol
 Drugs thatare primarily absorbed in the stomach
e.g. Amoxicilin
 Drugs that are poorly soluble at alkaline pH
e.g. Furosemide, Diazepam, Verapamil, etc.
 Drugs witha narrow windowof absorption
e.g. Cyclosporine, Methotrexate, Levodopa,
etc.
 Drugs whichare absorbed rapidly from the
GItract.
e.g. Metronidazole, tetracycline.
 Drugs thatdegrade in the colon.
 Drugs that cause gastric lesions.
E.g. NSAIDs.
 Drugs that undergo first pass metabolism.
E.g.
Nifedipine.
 Drugs that have very limited acid solubility
and stability.
E.g. Phenytoin.
 Drugs that degrade in acidic environment.
Eg . Insulin
 Density of dosage forms
Adensity of <1.0 gm/cm3 is required to exhibit
floatingproperty.

 Shape and size of the dosage form

Dosage forms having a diameter of more than 7.5 mm
show a better gastric residence time .
Ring-shaped and tetrahedron-shaped devices have a better
gastric residence time as compared with other shapes.

 Food intake and its nature

The presence or absence of food in the gastrointestinal tract
(GIT) influences the gastric retention time (GRT) of the
dosage form.
 Usual y the presence of food in the
gastrointestinal tract (GIT) improves the gastric
retention time (GRT) of the dosage form and
thus, the drugs absorption increases by allowing its
stay at the absorption site for a
longer period. Again, increase in acidity and
caloric value shows down gastric emptying time
(GET), which can improve the gastric retention of
dosage forms.
 Gender: Generally females have slower gastric
emptying rates than male.
 Age: In case of elderly persons, gastric
emptying is slowed down.

 Caloric content: GRT can be increased by 4

to 10 hours
with a meal that is high in proteins and fats.
 Floating – A low density approach
 Non-effervescent systems
 Effervescent systems
 Expandable approach
 Swelling systems
 Unfolding systems
 Bio-mucoadhesive approach
 High density approach
 Raft forming system
15
 These are low density
systems.<1.0g/cm3

 Have ability to float over gastric

contents.
1) Effervescent
 Volatile liquid containing systems

 Gas generating systems

2)Non-Effervescent
 Colloidal gel barrier systems

 Alginate beads

 Hollow Microspheres

 Microporous Compartment System

1) EFFEREVESCENT SYSTEMS

a) Gas generating systems

 Effervescence is there.

 Utilizes effervescent reactions between

carbonate/bicarbonate salts and citric/tartaric
acid.

 CO2 is released in presence of H2O.

 When tablet is put in beaker it will sink

 2NaHCO3+C4H6O6
C4H4Na2O6+2CO2+2H2O

With production of gas it rises up and floats.

 swellable polymers such as
methocel, (e.g., chitosan)
effervescent components (e.g., sodium
bicarbonate, citric acid or tartaric
acid)

 The system is so prepared that upon arrival in the stomach,

carbon dioxide is released, causing the formulation to float in
the stomach.
b) Volatile liquid containing system:
 These type of systems consist of two chambers
separated by an impermeable, pressure-
responsive,movable bladder.
 The first chamber contains the drug and the
second chamber contains the volatile liquid.
The device inflates, and the drug is
continuously released from the reservoir into
the gastric fluid .
 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 float
2) NON-EFFERVESCENT SYSTEMS

a) Colloidal gel barrier systems

 Such systems contains drug w ith gel
forming hydrocolloids meant to remain buoyant on
stomach
contents.

 These systems incorporate a high level of one or more gel

forming highly Swellable cellulose type hydrocolloids.
e.g.HEC, HPMC, NaCMC.

 On coming in contact with gastric fluids , hydrocolloid in the

system hydrate and form colloidal gel barrier around its
surface.

 Density of system falls below 1gm/cm 3 . Then it starts floating

b) Microporous compartment system
 The encapsulation of a drug reservoir inside a
microporous compartment with pores along its top
and bottom walls.
 The peripheral walls of the drug reservoir compartment
are completely sealed to prevent any direct contact
of gastric surface with the undissolved drug.
 In floatation chamber containing entrapped air causes
delivery system to float over gastric fluid.
 Gastric fluid enters through the aperture, dissolves the drug
and carries the dissolved drug for absorption.
c) Alginate beads
 Freeze dried calcium alginate beads are produce by
dropping sodium alginate solution into aqueous solution of
calcium chloride.

 gelation take place and forms solid spherical gel

beads, which are separated from solution and
they are freeze dried in liquid nitrogen at - 40oC for 24 hours.
The resultant weight of beads is less giving buoyancy up to
12 hours.

Sodium alginate+ Calcium chloride

Calcium alginate+ NaCl
d) Hollow microspheres

 Microballoons / hollow microspheres loaded with

drugs are prepared by simple solvent evaporation
method.

 Commonly used polymers to develop these

systems polycarbonate, cellulose acetate
,calcium
are alginate, Eudragit S , agar and pectin etc.
 Delivery device within the human toenhance
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 electrontheory.
 Materials commonly used for bioadhesion are poly
acrylicacid, chitosan, cholestyramine, sodium
alginate, hydroxypropyl methylcellulose (HPMC),
sucralfate, tragacanth, dextrin, polyethylene glycol
and polylactic acids etc.
1) UNFOLDING
SYSTEM
These systems are made of biodegradable polymers and
are
capable of being mechanically increased in size relative to
the initial dimensions.
 After being swallowed, these dosage forms swell to a size that
prevents their passage though rough the pylorus and therefore,
the dosage form is prone to be retained in the stomach for a long
period of time.
2) SWELLING SYSTEMS

 These are the dosage forms, which after

swallowing, swells to an extent that prevents
their exit from the pylorus.
 These systems may be named as ‘plug type
systems’, since they exhibit the tendency to remain
logged at the pyloric sphincter if that exceed a
diameter of approximately 12-18mm in their
expanded.
 Chitosan, HPMC, sodium Starch glycolate,
Carbapol are used.
 Gastric contents have a density close to water.
 A density close to 2.5g/cm3 is necessary
for significant prolongation of gastric

residence time.

 The commonly used excipients in high

density system includes
barium sulphate, zinc oxide, iron powder,
and titanium dioxide.
 The major drawback with such systems is that it is technically
difficult to manufacture them with a large amount of drug
(>50%) and to achieve the required density.
 Raft forming systems have received antacids and drug
delivery for treatment of gastrointestinal infection and
disorders.

 The mechanism involved in this system included

the formationof viscous gel in contact with gastric
fluids, wherein each portion of the liquid swells, 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 (sodium alginate) and
alkaline bicarbonates or carbonates responsible for the
formation of CO2 to make the system less dense to float
on the gastric fluids.
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.
ii) Swelling systems
a) Swelling Index
After immersion of swelling dosage form into SGF at 37C,
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.
Water uptake = WU = (Wt –Wo) * 100 / Wo
Where, Wt = weight of dosage form at time t Wo = initial
weight of dosage form
 Radiology

 Scintigraphy

 Gastroscopy

 Magnetic
MarkerMonitoring

 Ultrasonography

 13C Octanoic Acid Breath

Test