Gastroretentive
Drug Delivery
System
Dr Yasser Shahzad
Gastroretentive drug delivery system (GRDDS)
Gastroretentive drug delivery is an
approach to prolong gastric residence
time, thereby targeting site-specific drug
release in the upper gastrointestinal
tract (GIT) for local or systemic effects.
Need for GRDDS
Oral drug delivery systems generally suffer from mainly two adversities:
a) Short gastric retention time(GRT)
b) 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.
Potential drug candidates for GRDDS
1. Drugs acting locally in the stomach (active in stomach), e.g. Antacids and drugs
for H. Pylori viz., Misoprostol
2. Drugs that are primarily absorbed in the stomach, e.g. Amoxicillin
3. Drugs that are poorly soluble at alkaline pH, e.g. Furosemide, Diazepam,
Verapamil, etc.
4. Drugs with a narrow window of absorption, e.g. Cyclosporine, Methotrexate,
Levodopa, etc.
5. Drugs which are absorbed rapidly from the GI tract, e.g. Metronidazole,
tetracycline.
6. Drugs that degrade in the colon, e.g. Ranitidine, Metformin HCl.
7. Drugs that disturb normal colonic microbes, e.g. antibiotics against Helicobacter
pylori.
Drugs unsuitable for gastroretention
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.
Factors affecting the gastroretentive system
1. Density 7. Frequency of feed
2. Size 8. Gender
3. Shape of dosage form 9. Age
4. Single or multiple unit 10. Posture
formulation
11. Concomitant drug
5. Fed or unfed state
6. Nature of meal
Advantages
• Improved drug absorption, because of increased GRT and more time
spent by the dosage form at its absorption site.
• Controlled delivery of drugs.
• Minimising mucosal irritation by releasing drugs slowly at a controlled
rate.
• Treatment of gastrointestinal disorders such as gastro-esophageal
reflux, providing local action.
• Ease of administration and better patient compliance.
Approaches to gastric retention
Floating drug delivery systems
The major requirements for floating drug delivery system are:
• Release contents slowly to serve as a reservoir.
• Maintain specific gravity lower than gastric contents
(1.004 – 1.01 gm/mL).
• Form a cohesive gel barrier.
The inherent low density can be provided by the entrapment of air
(e.g. hollow chambers) or by the incorporation of low density
materials, e.g. fatty materials or oils, or foam powder.
Multiple-unit floating system preferred over Single-unit dosage
because of dose dumping.
Floating techniques
– Effervescent
• Volatile liquid containing systems
• Gas generating systems
– Non-Effervescent
• Colloidal gel barrier systems
• Alginate beads
• Hollow Microspheres
• Microporous Compartment System
High density system
• These have density greater than that of gastric fluids (1.4 g/mL).
• Above 1.6 g/mL is preferable, tend to withstand peristaltic
movements of stomach.
• Zinc oxide, Iron oxide, Titanium dioxide, barium sulfate are used as
inert heavy core.
Bioadhesive or mucoadhesive systems
Delivery device within the human to enhance drug absorption in a site-specific
manner.
Bioadhesive polymers used which adhere to the epithelial surface in the
stomach & improves the prolongation of gastric retention.
The mechanisms are:
1) The wetting theory, which is based on the ability of bioadhesive polymers to
spread and develop intimate contact with the mucous layers.
2) The diffusion theory, which proposes physical entanglement of mucin strands
with the flexible polymer chains, or an interpenetration of mucin strands into the
porous structure of the polymer substrate.
3) The absorption theory, suggests that bioadhesion is due to secondary forces
such as Van der Waal forces and hydrogen bonding.
4) The electron theory, which proposes attractive electrostatic forces
between the glycoprotein mucin net work and the bioadhesive material.
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.
Superporous hydrogel systems
These swellable systems differ sufficiently from the conventional types
to warrant separate classification. In this approach to improve gastric
retention time (GRT) super porous hydrogels of average pore size >100
µm, swell to equilibrium size due to rapid water uptake by capillary
wetting through numerous interconnected open pores. They swell to a
large size (swelling ratio: 100 or more) and are intended to have
sufficient mechanical strength to withstand pressure by gastric
contraction.
Magnetic Systems
This approach to enhance the gastric retention time (GRT) is based on
the simple principle that the dosage form contains a small internal
magnet, and a magnet placed on the abdomen over the position of the
stomach. Although magnetic system seems to wok, the external magnet
must be positioned with a degree of precision that might compromise
patient compliance
Conclusion
Gastro retentive drug delivery systems are the most preferable systems
in order to deliver the drugs which have a narrow absorption window
near the gastric region. Now a days a number of drug delivery devices
are being developed which aim at releasing the drug at gastric region.
Even though these drug delivery systems have several advantages they
also have disadvantages like their in vitro – in vivo correlation is very
less.
