GASTRO RETENTIVE DRUG
DELIVERY SYSTEM
• Oral route of drug administration is the most
convenient and commonly used method of drug
delivery
• Dosage forms that can be retained in the stomach
are called gastro retentive drug delivery systems
(GRDDs)
• GRDDSs can improve the controlled delivery of
drugs that have an absorption window by
continuously releasing the drug for a prolonged
time before it reaches its absorption site
• Gastrointestinal transit is the time for food to
move from the stomach to the intestine.
• Controlling gastric residence time (GRT)
allows for prolonged, predictable drug
delivery.
• Extended gastric retention improves
bioavailability, reduces drug waste, and
increases solubility.
• GRT is useful for target-specific drug release.
• GRT is primarily achieved by delaying gastric
emptying.
ADVANTAGES
• Enhanced bioavailability for drugs absorbed in the upper GIT
(riboflavin, L-Dopa).
• Sustained drug release, reducing dosing frequency and improving
compliance.
• Reduced fluctuations in plasma drug concentrations.
• Targeted therapy for local ailments in the stomach and small intestine.
• Site-specific delivery minimizes systemic exposure and side effects.
DISADVANTAGES
• Unsuitable for drugs with limited acid solubility Eg: Phenytoin
• Unsuitable for drugs that are unstable in an acidic environment
E.g. Erythromycin
• Drugs that irritate or cause gastric lesions on slow release
E.g. Aspirin & NSAIDs
• Drugs that absorb selectively in colon
E.g. Corticosteroid
• Drugs that absorb equally well through GIT
E.g. Isosorbide dinitrate, Nifedipine
• Floating drug delivery systems require high fluid level in the stomach
to float and work effectively
PHARMACEUTICAL APPROACHES TO EXTEND GI TRANSIT TIME
CLASSIFICATION
FLOATING OR LOW DENSITY DRUG DELIVERY SYSTEMS
Floating drug delivery systems (FDDS) or hydrodynamically balanced systems
have a bulk density lower than gastric fluids and thus it is floatable in the stomach
without affecting the gastric emptying rate for a prolonged period
While the system is floating the drug is
released in a controlled rate and residual
system is emptied from the stomach
As a result there is increased
GR and less fluctuations in
plasma drug concentration
A. EFFERVESCENT SYSTEM
• Composition: Made of swellable polymers (methylcellulose, chitosan) combined
with effervescent compounds (sodium bicarbonate, tartaric acid, citric acid).
• Mechanism: Upon contact with gastric fluid, CO₂ is liberated, trapped in the swollen
hydrocolloid, making the system float.
• Design Basis: Uses a swellable asymmetric triple-layer tablet approach for
prolonged gastric retention and sustained drug release.
1. Gas generating systems
Effervescent reactions between
carbonate/bicarbonate salts and citric/tartaric
acid release CO₂.
The CO₂ gets trapped in the hydrocolloid layer,
making the system float on gastric fluid.
a) Single Layer Floating Tablets or Hydrodynamically Balanced Systems (HBS)
• CO₂-generating agents and the drug are mixed in a matrix tablet,
allowing slow and controlled drug release.
• The system increases gastric retention time (GRT) and stabilizes
plasma drug concentration.
b) Bilayer Floating Tablets
These are compressed tablet containing two layer
(1)Immediate release layer
(2) Sustained release layer
c) Multiple Unit Type Floating Pills
• Composed of sustained-release pills surrounded by an effervescent
inner layer and a swellable outer membrane.
• Upon immersion, the system initially sinks, then swells and floats due
to CO₂ generation and entrapment.
• Floating is achieved through reduced density caused by the trapped
CO₂ within the system.
d) Floating systems with Ion exchange resin
• Resin beads loaded with bicarbonates are coated with water-
permeable ethyl cellulose, allowing ion exchange in the
stomach.
• CO₂ generated from bicarbonate reacts with chloride ions, gets
trapped in the polymer, and enables the beads to float.
2. Volatile liquids/vacuum systems
An inflatable chamber with gasifying liquids (e.g., ether,
cyclopentane) prolongs gastric retention by inflating at
body temperature.
A bio erodible plug dissolves over time, releasing gas and
collapsing the system for ejection from the stomach.
a) Intragastric Floating Gastrointestinal Drug Delivery System
• A floatation chamber (vacuum, air, or gas) enables the GIDS to float
in gastric fluids.
• The drug reservoir is enclosed in a microporous compartment,
preventing direct contact with the stomach lining.
• Gastric fluids dissolve the drug, which is released through apertures
for continuous intestinal absorption.
b) Inflatable Gastrointestinal Drug Delivery System
• An inflatable chamber with liquid ether gasifies at body
temperature, causing stomach inflation.
• The chamber contains a drug reservoir, encapsulated in a
gelatin capsule that dissolves after oral administration.
• Upon release, the chamber inflates, retaining the drug
reservoir in gastric fluid for prolonged delivery.
c) Intragastric Osmotically Controlled Drug Delivery System
• Contains an osmotic drug delivery device and an inflatable
floating support within a bioerodible capsule.
• The capsule disintegrates in the stomach, releasing the
device, while the support inflates via gasification of its
liquid content.
[Link] EFFERVESCENT SYSTEM
Non-effervescent FDDS is based on mechanism of swelling of polymer or bioadhesion to
mucosal layer in GI tract
Various type of this systems are :
1. Single layer floating tablets
2. Bilayer floating tablets
3. Alginate beads
4. Hollow microspheres
a) Single layer floating tablets
The drug is formulated by intimately mixing with a gel-forming hydrocolloid like HPMC,
which swells upon contact with gastric fluid, maintaining a bulk density of less than unity.
b) Bilayer floating tablets
A bilayer tablet consists of an immediate release layer for the initial dose and a sustained
release layer that absorbs gastric fluid, forming an impermeable gel barrier, maintaining a
bulk density of less than unity, and remaining buoyant in the stomach.
c) Alginate beads
Multi-unit floating dosage forms using freeze-dried calcium alginate are prepared by dropping
sodium alginate into calcium chloride solution, forming 2.5 mm spherical beads with a porous
structure that maintain floating force for over 12 hours.
d) Hollow microspheres
• Hollow microspheres loaded with drug were prepared using an emulsion-solvent
diffusion method with an acrylic polymer and PVA solution.
• Gas formation during evaporation created cavities, allowing the microballoons to float
for over 12 hours in acidic media.
BIO(MUCO)ADHESIVE GASTROINTESTINAL DRUG DELIVERY SYSTEMS
• Mucoadhesive polymers adhere to the gastric mucosal surface,
prolonging retention in the GIT.
• Useful excipients in gastric retention drug delivery systems
(GRRDS).
• Natural polymers: sodium alginate, gelatin, guar gum.
• Semisynthetic polymers: HPMC, Carbopol, sodium
carboxymethyl cellulose.
A bio(muco)adhesive polymer is known to have the following
molecular properties:
1. It has molecular flexibility
2. It contains hydrophilic functional groups
3. It poses a specific molecular weight, chain length, and
conformation
• Bonding established between the polymer and mucosal surface facilitates the
mucoadhesion process, which generally involves two steps: the contact stage and the
consolidation stage
HIGH DENSITY SYSTEM
• Non-floating drug delivery system.
• Sedimentation is the retention mechanism. Formulations
must have a density greater than 1.004 g/ml.
• Prepared by coating drug on a heavy core or mixing with
inert materials (iron powder, zinc oxide, titanium dioxide,
barium sulfate).
• Pellets can be coated with a diffusion-controlled
membrane.
• Drawback: Difficult to manufacture with large drug
amounts due to interaction with gastric fluid, releasing
drug contents.
APPLICATIONS
• Prolonged Drug Release: Increases the residence time of the drug in the stomach,
providing sustained release for extended therapeutic effects.
• Improved Bioavailability: Enhances absorption of drugs that are absorbed mainly in
the stomach or upper part of the small intestine.
• Targeted Therapy: Allows localized drug delivery in the stomach for conditions like
peptic ulcers or gastritis.
• Reduced Dosing Frequency: Prolongs the drug’s therapeutic action, leading to reduced
dosing frequency and improved patient compliance.
• Management of Drugs with Narrow Therapeutic Index: Helps in maintaining
consistent drug levels in the body for drugs with narrow therapeutic windows.
• Treatment of Helicobacter pylori Infection: Effective in delivering
antibiotics or antiulcer agents to the gastric mucosa.
• Gastrointestinal Disorders: Useful for treating conditions like
gastroesophageal reflux disease (GERD) and motility disorders.
• Antidiabetic Drugs: Delivers antidiabetic agents over an extended
period, improving glucose control and reducing peaks in blood sugar
levels.
REFERENCE
• Das, S., Kaur, S. & Rai, V.K. Gastro-retentive drug delivery systems: a
recent update on clinical pertinence and drug delivery. Drug Deliv. and
Transl. Res. 11, 1849–1877 (2021).
[Link]
• hao S, Lv Y, Zhang JB, Wang B, Lv GJ, Ma XJ. Gastroretentive drug
delivery systems for the treatment of Helicobacter pylori. World J
Gastroenterol. 2014 Jul 28;20(28):9321-9. doi:
10.3748/wjg.v20.i28.9321. PMID: 25071326; PMCID: PMC4110563.
