Gastro rententive drug

delivery system
Submitted to:
Dr. B. Wilson
Head of the Department,
Department of Pharmaceutics,
College of Pharmaceutical Sciences, DSU
Dayananda sagar college of Pharmacy,
Banglore.
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 Content
s• Introduction
• Appropriate drug candidate for GRDDS
• Factors affecting GRDDS
• Advantages and disadvantages
• Approaches to GRDDS
• References

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Introduction
 Oral route is extensively used, but not all drugs are uniformly
absorbed throughout GIT.
 Drugs released after absorption window has no or negligible
absorption. This can be overcome by retaining drug in
stomach.
 Gatro rententive drug delivery (GRDDS) is one of the site
specific drug delivery for the delivery of drugs at stomach.
 It is obtained by retaining dosage form into stomach and drug
is being released at controlled manner at specific site.
 GRDDS is an approach to prolong gastric residence time, there
by targetting site specific drug release in the upper
gastrointestinal tract (GIT) for local and systemic effect.

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 Appropriate candidate 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. Furosemide, Diazepam, Verapamil etc.
 Drugs with a narrow window of absorption
e.g. Cycloserine, Methotrexate, Levodopa etc.
 Drugs which are absorbed rapidly from the GIT
e.g. Metronidazole, tetracycline.
 Drugs that degrade in the colon. e.g. Rantidine, Metformin HCl.
 Drugs that disturb normal colonic microbes.
e.g. antibiotics against H. Pylori.
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 Drugs that are unsuitable for GRDDS
 Have that have very limited acid solubility.
e.g. phenytoin etc
 Drugs not stable in the gastric region.
e.g. Erythromycin etc.
 Drugs intended for selective release in the colon.
e.g. 5- amino salicylic acid and corticosteroids.

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 Physiology of the GIT
• The GI tract is essentially a
tube about nine metres long
that runs through the middle
of the body from the mouth to
the anus and includes
the throat (pharynx),
oesophagus, stomach, small
intestine (consisting of the
duodenum, jejunum and
ileum) and large intestine
(consisting of the cecum,
appendix, colon and rectum).

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• Drug absorption in the case of-
(a) Conventional dosage forms,
(b) Gastroretentive drug
delivery systems.

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Gastric Emptying
• Gastric emptying occurs during fasting as well as fed states.
• Gastric emptying occurs as a result of gastric contraction, the
nature of which depends on the contents of the stomach.
• Thus gastric emptying can be conveniently classified into gastric
emptying of liquid, digestible solids, and indigestible solids. Liquids
empty from the stomach as a result of Intragastric pressure
generated by slow muscular contractions occurring mainly from
the proximal stomach (i.e. the upper body of the stomach).
• The removal of liquid is First order, i.e., the volume of liquid
emptied per unit time is directly proportional to the volume
remaining in the stomach.
• Digestible solids are known to be emptied only when they have
been changed to a thick, creamy substance called chyme.
• Indigestible solids including oral dosage forms are known to be
emptied from the stomach in fasting state by a distinct cycle of
Myoelectrical activity known as the Interdigestive Migrating
myoelectric complex (IMMC).

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• Gastric This is called
motility:
the interdigestive myloelectric cycle or
migrating myloelectric cycle (MMC),
which is further divided into following 4
phases:-
1. Phase I (basal phase):lasts from 30 to
60 minutes with rare contractions.
2. Phase II (preburst phase):lasts for 20 to
40 minutes with intermittent action
potential and contractions. As the phase
progresses the intensity and frequency
also increases gradually.
3.Phase III (burst phase):lasts for 10 to 20minutes. It includes intense and
regular contractions for short period. It is due to this wave that all the
undigested material is swept out of the stomach down to the small
intestine. It is also known has housekeeper phase.
4.Phase IV: lasts for 0 to 5 minutes and occurs between phases III and I of
two consecutive cycles.
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• Gastrointestinal Transit Time
The residence time of liquid & solid foods in each segment of
the GI tract is different. Since most drugs are absorbed from
the upper intestine (duodenum, jejunum, and ileum), the
total effective time for drug absorption is 3-8 hrs. This is why
one has to take most drugs 3-6 times a day.
Type of food

Segment
Solid Liquid

Stomach 10-30mins 1-3hrs

Duodenum 60secs 60secs

Jejunum & ileum 3hr±1.5hr 4hr±105hr

Colon - 20-50hr

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 FACTORS CONTROLLING GASTRIC
RETENTION OF DOSAGE FORMS
• Density of dosage forms
A density of <1.0 gm/cm3 is required to exhibit floating property.
• Shape and size of the dosage form
Dosage forms having a diameter of more than 7.5 mm show a
better gastric residence time compared with one having 9.9 mm.
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.
Usually 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.

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• Fed or unfed state
Under fasting conditions: GI motility is characterized by
periods of strong motor activity or the migrating myoelectric
complex (MMC) that occurs every 2 to 3 hours. The MMC sweeps
undigested material from the stomach and, if the timing of
administration of the formulation coincides with that of the MMC,
the GRT of the unit can be expected to be very short. However, in
the fed state, MMC is delayed and GRT is considerably longer.
• 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.
• Disease state
Gastric ulcer, diabetes, hypothyroidism increase GRT.
Hyperthyroidism, duodenal ulcers decrease GRT.

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Advantages
• Improved drug absorption because of increased GRT.
• Enhanced bioavailability.
• Controlled drug delivery.
• Reduced dosing frequency.
• Ease of administration.
• Better patient compliance.
• Targeted therapy for local ailments in the upper GIT.
• Reduced fluctuations of drug concentration.
• Delivery of drugs with narrow absorption window
in small intestine region.
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Pharmaceutics 13
Disadvantage
• Retention in stomach is not desirable for drugs that cause
gastric lesions/irritations. e.g. NSAIDS.
• Drugs degraded in the acidic environment of stomach.
e.g. insulin.
• Drugs undergo significant first- pass metabolism.
e.g. nifedipine.
• Drugs have limited acid solubility. e.g.phenytoin.
• These systems require a high level of fluid in the stomach
for drug delivery to float and work efficiently.
• These systems do not offer significant over the
conventional dosage forms for drugs, which are absorbed
throughout GIT.
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 APPROACHES FOR PROLONGING THE
GASTRIC RESIDENCE TIME
1.High-density systems (HDS)
2.Floating systems. (FS)
3.Swelling and expanding
systems(SS)
4. Mucoadhesive &
Bioadhesive systems.

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1. High density system
• Gastric contents have a density close to water( 1.004
gm/ cm3). 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 gm/cm3 seems necessary for
significant prolongation of gastric residence time.
• Drawback is technically it is difficult to manufacture
such systems with high amount of drug (>50%) and to
achieve a density of about 2-8.
• Barium sulphate , zinc oxide, iron powder, and
titanium dioxide are examples for excipients used.

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 2. Floating system (low density)
•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:
a. Hydro dynamically balanced systems (HBS)
b. Gas-generating systems
c. Volatile liquid/ vacuum containing systems

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a. HYDRODYNAMICALLY BALANCED SYSYTEMS
• HBS/Colloidal barrier systems contain drugs with gel forming
hydrocolloids to float on stomach contents.
• This prolongs GI residence time and maximises drug reaching its
absorption site.
• Prepared by incorporating a high level(20-75%w/w) gelforming
hydrocolloids. E.g.:- Hydoxyethylcellulose, hydroxypropylcellulose,
HPMC & Sod. CMC into the formulation and then compressing
these granules into a tablets or capsules.
• maintains the bulk density less than 1.

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b. 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 over chyme.

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 c. Volatile liquid/ vaccum containing
system
• These systems contain an inflatable
chamber, which contains a liquid
(ether, cyclopentane), that gasifies at
body temperature to cause
inflatation of the chamber in
stomach.
• These are osmotically
devices
controlled floating systems
containing a hollow deformable unit
that can convert from a collapsed to
an expanded position, and returns to
collapsed position after an extended
period.

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 3.Swelling system
• A dosage form in the stomach will
withstand gastric transit if it bigger than
pyloric sphincter, but should be
small enough to be swallowed.
• These systems swells many times its
original size.
• Cross linking should be optimum
highly
cross linked don’t swell.
• Sustained and controlled release is
achieved by selection of proper
molecular weight polymer, and swelling
of polymer retards drug release.
• Chitosan, HPMC, sodium starch
glycolate, Carbopol are used.
• Diclofenac, Ciprofloxacin, Furosemide
are reported with these systems.
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 4. BIOADHESIVE OR MUCOADHESIVE
SYSTEMS
• Delivery device within the human to enhance 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 electron theory.
• Materials commonly used for bioadhesion are poly acrylic
acid, chitosan, cholestyramine, sodium alginate, hydroxypropyl
methylcellulose (HPMC), sucralfate, tragacanth, dextrin,
polyethylene glycol and polylactic acids etc.

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GRDDS Marketed drugs.

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References
• N. K. Jain, Progress in Controlled & Novel Drug
Delivery Systems, 1st edition 2004, CBS Publishers,
page no.76-86.
• International Journal of Pharma and Bio Sciences
GASTRORETENTIVE DRUG DELIVERY SYSTEM - A
REVIEW by RIZWANA KHAN* Institute of Pharmacy
Bundelkhand University, Jhansi , U. P., India.
• S. P. Vyas & R. K. Khar, Controlled drug delivery-
concepts and advances, Vallabha Prakashan
publishers, page no. 197- 217.

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