Department of Pharmaceutics
R. C. Patel Institute of Pharmaceutical Education and Research,
Mr. Roshankumar G.
drug delivary system
•Anatomy and Physiology of Stomach
•Need for gastro retention
•Suitable and Unsuitable Drugs for GR
•Approaches for GRDDS
•Factors Affecting DDS
Gastroretentive drug delivery is an approach to prolong gastric residence time,
targeting site-specific drug release in the upper gastrointestinal tract (GIT) for local or
Oral drug administration has been the predominant
route for drug delivery.
Gastric residence time is time which a drug resides in
Depends upon fluid and food intake.
GRDDS are designed to delay gastric emptying.
NEED FOR GRDDS
Oral drug delivery system and Sustained drug delivery systems
These drug delivery systems suffer from mainly two adversities:
1. short gastric retention time(GRT)
2. unpredictable short gastric emptying time (GET)
which can result in incomplete drug release from the dosage form in the absorption zone
(stomach or upper part of small intestine) leading to diminished efficacy of administered dose.
To formulate a site-specific orally administered controlled release dosage form, it is desirable
to achieve a prolong gastric residence time by the drug delivery. Prolonged gastric retention time
(GRT) in the stomach could be advantageous for local action e.g. treatment of peptic ulcer, etc.
SUITABLE DRUGS FOR GRDDS
• Drugs acting locally in the stomach.
E.g. Antacids and drugs for H. Pylori , Misoprostol.
• Drugs that are primarily absorbed in the stomach.
• 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.
UNSUITABLE DRUGS FOR GRDDS
1] Drugs That Have Very Limited Acid Solubility
E.g. Phenytoin, Etc.
2) Drugs That Suffer Instability In The Gastric Environment.
E.g. Erythromycin, Etc.
3) Drugs Intended For Selective Release In The Colon
E.g. 5-amino Salicylic Acid And Corticosteroids, Etc.
Anatomy and Physiology of Stomach
A tube about nine meters long that runs through the middle of
the body from the mouth to the anus and includes ;
The process of gastric emptying occurs both during fasting and fed state.
In fasted state, the process of gastric emptying is characterized by an interdigestive
motility pattern that is commonly called migrating motor complexes (MMC).
This is a series of events that cycle through the stomach every 1.2 to 2 hrs.
In fed state, the gastric emptying rate is slowed down because the onset of MMC is
delayed, i.e. the feeding state results in lag time prior to onset of gastric emptying.
30-60 min with infrequent contractions
20-40 min with the irregular action
potential and contractions as the phase
developments, the intensity and the
frequency also rises gradually
10-20 min, it contains intense and
regular contractions for short periods. It’s
due to this wave that all the undigested
material is swept from stomach to the
0-5 min and happens between phase
three & one of two successive cycles
FACTORS AFFECTING GRDDS
3. Shape of Dosage form
4. Single or Multiple Unit Formulations
5. Fed or Unfed state
6. Nature of meal
7. Caloric Content
8. Frequency of feed
12.Concomitant Drug Administration
A. Floating System
Floating system further classified as :-
a) Effervescent system
-Gas generating system
-volatile liquid containing system
-Colloidal gel barrier system
-Microporous compartment system
-Alginate floatinf beads
-Raft forming systems
a) Effervescent system:-
Matrix types of system prepared with the help of
swellable polymers such as methylcellulose and
chitosan and various effervescent agents such as
sodium bicarbonate, tartaric acid, and citric acid.
b) Non-Effervescent system
Colloidal gel barrier system (HBS)
Microporous Compartment System
Example: Floating and sustained release granules of diclofenac sodium.
Contents: HPC, ethyl cellulose, Ca silicate (floating carrier).
Mechanism: Ca silicate is coated with a polymer i.e. HPC. The air is trapped
in pores of Ca silicate when coated with polymer. Thus, they float.
Floating microspheres (Micro balloons)
Micro balloons or Hallow microspheres loaded with drug
prepared by solvent evaporation method.
Polymers used polycarbonate, cellulose acetate, calcium
alginate, agar, and low methoxylated pectin etc.
Buoyancy and drug release depends on quantity of
polymers, plasticizer polymer and solvent used.
Micro balloons floated continuously over the surface of
an acidic dissolution media containing surfactant for >12
Raft Forming System
These systems when come in contact with
gastric fluids swell and forms cohesive gel. This gel
is formed due to sodium alginate solution
containing carbonates or bicarbonates.
They form raft layer on the top of gastric contents
and slowly release drug in the stomach.
This system is mainly used in gastro oesophageal
reflux treatment with Liquid Gaviscon.
They are used for delivery of antacids (Aluminium
hydroxide/CaCO3), drugs for GI disorders and
B) Low density System
This system has less density than the
gastric contents and thus remains buoyant in stomach for
prolonged period of time.
The drug in the formulation is released slowly with a desired
rate as formulated.
This system increases gastric retention time and reduces
the fluctuations in concentration of drug in plasma, thus
improving oral bioavailability.
Drugs which are absorbed mainly through upper part of
stomach are most suitable candidates
High Density System
High density systems are retained in
antrum/rugae of stomach and are having density more than
the threshold density (3 gm/cm3). For manufacturing of
these systems various diluents like barium sulphate, titanium
dioxide, iron powder, zinc oxide etc. are used for coating.
Technically manufacturing of this system is difficult as it is
difficult to achieve such a high density.
C. Swelling and Expanding System
These are the systems, which on reaching to the
gastric environment swells and becomes larger in
Generally, when the gastric emptying occurs, all the
contents in gastric cavity are transferred to the
intestine through pyloric sphincter.
In the phase III of MMC, when housekeeper waves
are present, pyloric sphincter enlarges to 13-18 mm in
For dosage system to remain in gastric cavity
should swell more than size of pyloric sphincter to
retain in gastric environment for longer period of time,
even in fed state.
For the sustained and controlled release of drug,
swelling polymer is used which retards the drug
Swelling polymer when comes in contact with
gastric contents, imbibes water and swells due to the
presence of chemical/physical cross-links in the
hydrophilic polymer network.
This cross-link prevents the dissolution of polymer
by maintaining physical integrity of dosage form.
5. Bio/ Muco-adhesive System
These system bind to gastric epithelial cell surface or mucin of the stomach. This will
enhance the retention time of the drug formulation in the stomach. The natural or synthetic
polymers are used in the formulations which interact with mucin to form bio/muco-adhesive
Polymers showing adhesive mechanism with biological membrane are called bioadhesive
polymers and those showing adhesive mechanism with mucus lining of GI mucosal surface
are called mucoadhesive polymers.
Examples of Bioadhesive Polymers
PAA, chitosan, sodium alginate, HPMC, sucralfate, tragacanth, dextrin,
PEG. Natural hydrophilic polymers can also be used alone or in their appropriate
combinations in formulation of matrix tablets.
E.g.: locust bean gum, guar gum, karaya gum, xanthun gum etc.
Properties of ideal mucoadhesive polymers
Non-toxic, non-absorbable from GI tract.
It should have molecular flexibility, specific molecular weight, hydrophilic
functional groups, conformation and chain length.
It should form non-covalent bond with mucin-epithelial surface.
It should have quick adherence to moist surfaces.
It should easily incorporate drug.
It should offer no hindrance to drug release.
It should have specific site of attachment.
It should be easily available and economical.
Super porous Hydro gel System
These system show mechanism of capillary wetting
through the number of pores they have.
The average pore size is more than 100
micrometer. The system swells to very large size
and have swelling ratio 100 or more within a
minute after coming in contact with gastric fluid.
The system can withstand pressure exerted by
gastric contraction as having sufficient mechanical
Novel Approaches in Gastro-retentive Drug Delivery System
1. Ion Exchange Resins
2. Tablets with Hollow Cylinder
3. Unfolding System
4. Multilayer Flexible Film
5. Floating In-Situ Gel
6. Dual Working System
7. Floating Pulsatile System
• Gastro retentive drug delivery systems have emerged as a current approach of
delivery of drugs that exhibit an absorption window.
• All these drug delivery systems have their own advantages and drawbacks.
• To design a successful GRDDS, it is necessary to take into consideration the
properties of the drug, physiological events in the GIT, formulation strategies, and
correct combination of drug and excipients.