Gastro Retentive

Drug Delivery
System
Presented By:
Dr. M. Waqas Ilyas
 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.

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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 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 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.

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Unsuitable Candidate Drugs for GRDDS
 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.
e.g . Insulin

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Physiology Of Gastro Intestinal Tract
The GI tract is essentially a tube about
nine meters 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) Gastro retentive 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.

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Gastric Emptying
• 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).
Gastric Motility
This is called 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.

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Gastric Motility
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 as 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
Density of dosage forms: Density of <1.0 gm/cm is required to exhibit
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Forms
1.
floating property.
2. 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.
3. Food intake and its nature: The presence or absence of food in the GIT
influences the GRT of the dosage form.
Usual y the presence of food in the GIT improves the GRT of the
dosage form and thus, the drugs absorption increases by allowing its
stay at the absorption site for a longer period.

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Factors Controlling Gastric Retention Of Dosage
Forms
Again, increase in acidity and caloric value shows down gastric
emptying time, which can improve the gastric retention of dosage
forms.
4. Gender: Generally females have slower gastric emptying rates
than male.
5. Age: In case of elderly persons, gastric emptying is
slowed down.
6. 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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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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Disadvantages
• 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
1. High-density systems (HDS)
Residence Time
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
A densitywall.
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
a. Hydrodynamically Balanced Systems
• HBS/Colloidal barrier systems contain drugs with gel forming
hydrocolloids to float on stomach contents.
• This prolongs GI residence time and maximizes drug reaching its
absorption site.

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2. Floating System (Low Density)
• 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.
• 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 devices are osmotically 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.
• 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 System
• 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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4. Bioadhesive or Mucoadhesive System

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Commercially available gastro retentive
formulations

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Thanks!
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