Gastroretentive Drug Delivery System

BY:
PROF. (DR.) JAVED ALI

DEPARTMENT OF PHARMACEUTICS,
SCHOOL OF PHARMACEUTICAL EDUCATION AND
RESEARCH JAMIA HAMDARD,NEW DELHI- 110062
E. MAIL: JALI@JAMIAHAMDARD.AC.IN
Gastroretentive drug delivery systems

❑ Introduction,

❑ Advantages,

❑ Disadvantages,

❑Approaches & Applications of GRDDS –

❑Floating,
❑High density systems,
❑Inflatable and
❑Gastroadhesive systems
 LEARNING
OUTCOMES
The learners will be able to identify
➢Need for Gastroretentive Drug Delivery Systems
(GRDDS)
➢Advantages and Disadvantages
➢Different types of GRDDS
➢Various approaches for design and development of
NDDS
➢Evaluation
➢Applications of GRDDS
➢Marketed GRDDS
 Reflection spot
What is the need/importance of developing
Gastroretentive Drug Delivery Systems?
 Introduction
❖Peroral drug delivery by conventional formulations widely
utilized.
❖The lack of efficacy of certain drugs due to decreased
bioavailability, unpredictable and erratic absorption, low
absorption window has prompted the examination of other novel
drug delivery systems.
❖One of them is the inability to confine the dosage form in the
desired area of GIT and thus controlling the GI transit time.
❖Drugs released from devices that achieve gastric retention would
be emptied with the gastric contents over a prolonged period and
would thus be present at the main absorption site, the small
intestine, for a longer time thus improvement in bioavailability
and reduce drug wastage.
Advantages from Drug Delivery point of view

▪ Sustained drug delivery

significantly prolong the gastric residence time of drugs.
▪ Site-specific drug delivery
Drugs, which have limited absorption sites in the upper small
intestine. For example, furosemide.
▪ Pharmacokinetic advantages
Drugs that have poor bioavailability because their absorption is
restricted due to the upper gastrointestinal tract can be delivered
efficiently, thereby improving their bioavailability by maximizing
their absorption.
 The drug candidate for development of Gastroretentive Drug
Delivery Systems
✓ Less soluble in the higher-pH environment of the small
intestine. E.g., weak bases such as chlordiazepoxide and
cinnarizine.
✓ Degraded by the pH conditions of the small intestine such as
captopril.
✓ For local drug delivery leading to high drug concentration to
the gastric mucosa and proximal small intestine. E.g., local
delivery of misoprostil.
✓ With low absorption windows. These drugs are taken up only
from very specific sites of G. I., often in a proximal region of
small intestine. E.g., Furesemide, cyclosporin, allopurinol and
ciprofloxacin.
Thus
❑Gastroretentive drug delivery systems (GRDDS)
are retained in the stomach for a prolonged period
of time.

❑ Are continuous release delay transit system which

can improve the control delivery of drug that have
an narrow absorption window.
 Advantages of GRDDS

➢ Improved drug bioavailability and therapeutic efficacy

➢ Reduced Drug Dose
➢ Sustained drug release and reduced dosing frequency
thus improving patient compliance.
➢Suitable for drugs that degraded in intestine or colon e.g.
Ranitidine hydrochloride
➢Good for drugs that required local action and that
primarily absorbed through the stomach e.g. Antacids and
Ferrous salt
 Continued…
➢Reduced adverse drug effects

➢Maintenance of constant therapeutic levels over a

prolonged period thus Reduction in fluctuation in
therapeutic levels minimizing the risk of resistance

➢ Improved Pharmacological effects of drugs

 Disadvantages of GRDDS

❖Requires food to delay gastric emptying

❖ Requirements of high fluid level in stomach
❖High turns over rate of mucous
❖ Not suitable for Drugs
✓irritant to gastric mucosa
✓Undergoes first pass metabolism
✓unstable under acidic condition
✓ Drugs having solubility and stability problem in GIT
 Continued…
➢More water uptake in floating systems as they require
high level of fluids in stomach for floating and working
efficiently.
➢Requires food to delay gastric emptying
➢Bioadhesive systems have problem of high turnover rate
of mucus layer
➢Presence of foods, gastric motility and pH that affects the
gastric retention
 Factors that Affects
gastric retention

❖Density ❖Feeding Frequency

❖Size ❖Gender
❖Shape of dosage form ❖Age
❖ Fed or unfed state ❖Formulation type
❖Nature of meal ❖Posture
❖Concomitant drug ❖Biological factors
administration
 Drug absorption
conventional v/s gastro retentive
 Stomach Physiology
Four major types of secretory epithelial cell

Mucous cells- secrete alkaline

mucus

Parietal cells – secrete HCL

Chief cells- secrete pepsin

G-cells- secrete hormone

gastrin
 GIT motility pattern
affecting dosage form retention
GASTRORETENTIVE TECHNIQUES
Classification
1. High densityDrug Delivery System
2. Floating Drug Delivery System
a) Hydrodynamically balanced system
b) Gas generating system
c) Volatile liquid vaccum containing system
i. Intragastric gastrointestinal drug delivery system
ii. Inflatable gastrointestinal delivery system
iii.Osmotically controlled drug delivery system
d) Raft forming system
e) Hollow microsphere
f) Alginate beads
g) Novel delivery system
3. Superporous hydrogels
4. Expanding systems
5. Bio/Muco-adhesive system
6. Magnetic System
 1) High Density System

➢Formulating Dosage forms that have higher density (3

g/ml) than normal stomach content (1.004 g/ml) and
capable of withstand peristaltic movement.
➢Inert materials like iron powder, barium sulfate , zinc
oxide, titanium dioxide enhanced density and retention
period
2) Floating Drug Delivery System
Floating Drug Delivery
System

Effervescent Non-Effervescent
System System

Gas Generating
system Volatile Liquid Colloidal Gel
Containing System (Hydrodynamically
Single Layer Floating Balanced System)
Tablet Intragastric gastrointestinal
Delivery System Single Layer Floating
Bilayer Floating Tablet Tablet
Inflatable gastrointestinal
Multiple unit pills Bilayer Floating Tablet
Delivery System
Floating system with Ion Hollow Microsphere
Exchange Resin Intragastric Osmotic
Controlled Delivery System Alginate Beads
 Non-Effervescent System
a) Hydrodynamically balanced
system
➢ Also termed as Colloidal gel system that contains gel forming
hydrocolloids e.g. HPMC, hydroxyethyl cellulose (HEC),
polycarbophil, polyacrylate, polystyrene etc. which remain
buoyant on the stomach content
 b) Gas Generating System

Single layered Floating Tablet

✓ Single layer Tablet have less bulk density than gastric content
✓ Achieve buoyancy in stomach unflattering gastric emptying rate
for long period.
✓ Sustained release of drug from matrix tablet at a desired rate.
 Bi-layered Floating Tablet
➢ Bi-layered tablet contains gas generating mechanism within one
hydrocolloid having sustained release layer and immediate
release layer
Multiple unit type Floating Pill

Mechanism of multiple floating pill

 c) Volatile Liquid Containing System
i) Intragastric gastrointestinal Delivery
System
➢Consisted of a flotation chamber filed with vacuum or
air or gas, and its incorporation into a microporous
compartment which houses the drug reservoir
 ii) Inflatable gastrointestinal Delivery
System

➢ Inflatable chamber contains liquid ether-gasifies at

body temperature to cause the chamber to inflate in
stomach.
➢ Inflatable chamber
is loaded with a drug
reservoir which can
be a drug, impregnated
polymer then encapsulated in a gelatin capsule.
 iii) Intragastric Osmotic Controlled
Delivery System
1. Drug Reservoir enclosed with
pressure responsive collapsible bag
and drug delivery orifice
2. Osmotically active compartment
enclosed with a semipermeable
housing with osmotically active
salts
➢Disintegration of capsules and release
of drug from the drug reservoir
through drug delivery orifice due to
generated osmotic pressure
 d) RAFT FORMING
• This system is used for delivery of
antacids and drug delivery for
treatment of gastrointestinal infections
and disorders.
• The mechanism involved in this
system includes the formation of a
viscous cohesive gel in contact with
gastric fluids, forming a continuous
layer called raft.
28
 e) Hollow Microspheres
(Microballons)
➢ Prepared using solvent evaporation or
solvent diffusion/evaporation method
➢Drug release and Buoyancy depend on
polymer quality plasticizer-polymer ratio
and solvent
➢ Commonly used Polymers:
Polycarbonates, Cellulose acetate,
Calcium alginate, Eudragit S, agar and
methoxylated pectin etc.
 f) Alginate Beads
➢Prepared using low methoxylated
pectin or Ca ions low methoxylated
pectin and sodium alginate

➢ Dropping of Sodium alginate

solution to calcium chloride
aqueous solution causing calcium
alginate precipitation.
 g) Novel Techniques

✓Prepared to retain the drug in the stomach more than 8

hours.

✓Provide instant and then sustained Release of drug for

long period

✓Can be used once in a day

 Oleotec and Soctec
✓Oleotec is a stick loaded gel that forms a continuous
pattern on the layer of the stomach material

✓Soctec has been established for drugs to be kept in the

stomach for large period of time.

✓Used for drugs that have narrow absorption window

✓For drugs which demands high dose

 Accordion Pill
✓Drug is compressed to compact capsule
✓Capsules melts into the stomach and release the drugs up
to 12 hours under frequent diets with calories.
✓Controlled delivery of drug to the top git portion
 3) Super porous hydrogel systems

➢ Pore size ranging from 10 nm to 10µm

➢Swell within a minute to reach equilibrium due to rapid

water uptake by capillary wetting

➢Achieved by co-formulation hydrophilic particulate material

and Ac-Di-Sol (cross-carmellose)
 4) Expanding System

✓ Composed biodegradable
polymers
✓ Preparation of carrier such as
capsule that extends in
stomach
✓ Swellable system retain in git
owing to their mechanical
properties
 5) Mucoadhesive System

▪Improved GRT by adhesion to mucin-epithelial surface

via

✓Hydration-mediated adhesion

✓Bonding-mediated adhesion

•Physical-mechanical bond and Chemical bond

✓Receptor mediated
 Continued…
❑ Bioadhesive
polymers
✓ Cationic: Polybrene,
Polylysine,
✓ Anionic: Polyacrylic
acid, Carrageenan
✓ Neutral: Dextran,
PEG, Polyethylene
pyrrolidone
 6) Magnetic System

❖ Dosage form composed a small internal magnet and a

external magnet placed on abdomen

❖ External magnet positioned with a degree of precision

❖ Enhanced Gastric residence time

❖ Ito et al. deliver bioadhesive granules in rabbit to the

esophagus using an external magnet
 EVALUATION PARAMETERS

➢Size and shape evaluation

➢Buoyancy/Floating test

➢Swelling Studies

➢Water uptake study

➢Drug Release
 Application of GRDDS

❖Absorption Enhancement
❖Site-specific Delivery
❖Bioavailability Enhancement
❖ Sustained Delivery
❖Minimized Adverse Activity at the Colon
❖Reduced Drug Concentration Fluctuations
 Marketed Formulation
Active Ingredients Products Technology Company
Diazepam Valrelease Floating capsule Roche, UK
Misoprostol Cytotec Bilayer floating capsule Pharmacia
Limited, UK
Metformin HCl Riomet OD Effervescent floating Ranbaxy, India
system
Ofloxacin Zanocin OD Effervescent floating Ranbaxy, India
system
Baclofen Baclofen GRS Multi-layer floating Sun Pharma,
& swelling system India
Ciprofloxacin Cifran OD Effervescent floating Ranbaxy, India
system
Tramadol Tramadol LP Minextab Floating® Galenix, France
 Marketed Formulation
Active Ingredients Products Technology Company
Cefaclor Cefaclor LP Minextab Floating® Galenix, France
Metformin HCL Metformin Minextab Floating® Galenix, France
HCL
LP
Aluminium Opalkan Floating liquid Pierre Fabre
magnesium antacid alginate Medicament,
France

*EUDRATEC ® GRS: an Evonik patent-pending

product for increasing nutritional supplement gastro
retention*.
Thank You