GASTRORETENTIVE DRUG

DELIVERY SYSTEM

Submitted to:DR .SUMAIRA

Submitted by: group 6 and 7
What is GRDSS?
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 system
• Sustained drug delivery systems
These drug delivery systems suffer from mainly two adversities:
• short gastric retention time(GRT)
• 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 .

Gastric Retention is done for:

 Drugs that absorb from stomach ( Levodopa, Furosemide).
• Acting locally in stomach (Antacids, Antiulcer and Enzymes).
• Poorly soluble at alkaline pH.( Diazepam, Salbutamol)
• Degrade in colon. (Captopril, Ranitidine, Metronidazole)
• Narrow window of absorption

Stomach:

 The stomach is an organ with a capacity for storage and mixing. The antrum
region is responsible for the mixing and grinding of gastric contents.
APPROACHES FOR GASTRIC RETENTION :
• High density systems
• Floating drug delivery systems
• Mucoadhesive sysytem
• Swellable systems
High density systems
Prepare by mixing or coating the drug with heavy inert material.

• These have density greater than that of gastric fluids (1.4 g/cm3)
• Zinc oxide, Iron oxide, Titanium dioxide, barium sulfate are used as
exicipents,which basically impart high density character to dosage form

Floating drug delivery system:

 Release contents slowly to serve as a reservoir.
• Maintain specific gravity lower than gastric contents (1.004 – 1.01 gm/cm3).
Floating techniques
Effervescent
• Gas generating systems
Non-Effervescent
• Colloidal gel barrier systems
• Alginate beads
• Hollow Microspheres
• Microporous Compartment System
NON-EFFERVESCENT SYSTEMS:
1. Colloidal gel barrier systems:
Such systems contains drug with 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,
Density of system falls below 1gm/cm3 . Then it starts floating.

2.Alginate beads:
• Spherical beads of approximately 2.5 mm in diameter can be prepared from
• sodium and calcium alginate.
• Maintain a floating force of over 12 hours

3. Hollow microspheres:
Microballoons / hollow microspheres loaded with drugs are prepared by simple
solvent evaporation method. Commonly used polymers are polycarbonate,
cellulose acetate, agar and pectin etc.
These systems have capacity to float 12 hours.
4. Microporous membrane systems:
Based on the encapsulation of drug reservoir inside a Microporous compartment.
• The peripheral walls of the drug reservoir compartment are completely
sealed gastric fluid enters through the apertures, dissolves the drug, and
carries the dissolve drug for absorption

MUCOADHESIVE SYSTEMS:
• Delivery device within the human to enhance drug absorption in a site-
specific manner.
• Muco adhesive polymers used which adhere to the epithelial surface
in the stomach & improves the prolongation of gastric
retention.Polymers use are poly acrylic acid, chitosan, cholestyramine,
sodium alginate,dextrin etc .
SWELLABLE SYSTEMS:
• 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. Swellable material
used are Chitosan, HPMC,Na starch glycolate etc.
 Diclofenac , Ciprofloxacin, Furosemide are reported with these systems
Characterization:
• Particle size:
should be in the range of 1-2mm to pass through the pyloric valves into
the small intestine.
• Density:
Density of dosage form should be in range of 1g/cm3 to 2.5g/cm3.
• Size:
size should be greater than 7.5mm in diameter.
• Prolong gastric rentention: Longer residence time in the stomach could be
beneficial for locl action in the upper part of small intestine.

• Increased bioavailability: Bioavailability of drugs improved which

ultimately gives improved therapeutic efficacy. Hence reduces frequency of
dosing.
• Site specific drug delivery: It have application for local or site specific
areas of stomach and proximal small intestines .

Stability:

• To Avoid dose dumping: For this multiple unit floating system is preferred.
Based on the mechanism of buoyancy. Excipients used in formulation for
this purpose are HPMC, polyacrylates, polyvinyl acetate, carbopol, agar,
sodium alginate, calcium chloride etc.

• Sufficient volume of media: GRDDS required a sufficient amount of media

in the stomach for the floating and work competently on the systems.
Sufficient amount of water (200-250ml) need to be administered for efficient
of working FDDS.
 • High Density: High density should be maintained to withstand
peristaltic waves.
• Size: It is important in swellable system. Size of formulation more than
pyloric sphincter.It should expand for gastric retention.
Others: food intake,nature of food and frequency,disease state affect the
formulation.

Advantages:
• Improved drug absorption, because of increased GRT and more time spent
by the dosage form at its absorption site.
• Controlled delivery of drugs.
• Minimizing mucosal irritation by releasing drugs slowly at a controlled rate.
• Treatment of gastrointestinal disorders such as gastroesophageal reflux,
providing local action.
• Ease of administration and better patient compliance

Limitations:
• Retention in the stomach is not desirable for drugs that cause gastric lesions
(e.g. Non- steroidal anti-inflammatory drugs NSAIDs).
• Drugs that are degraded in acidic environment of stomach (e.g. Insulin).
• Drugs that undergo a significant first-pass metabolism (e.g. Nifedipine).
• Drugs that have very limited acid solubility (e.g. Phenytoin).
GASTRORETENTIVE PRODUCTS AVAILABLE IN THE
MARKET:

BRAND NAME INGREDIENT

Cifran OD ciprofloxacin

Tolpalkan Aluminium magnesium antacid

valrelease diazepam
conviron ferrous sulphate
Liquid gavison Aluminium hydroxide
cytotec misoprostol