The document discusses gastroretentive drug delivery systems (GRDDS). It covers approaches to GRDDS including low density floating systems, high density systems, and mucoadhesive systems. It also discusses release kinetics, commonly used drugs and polymers, products available in the market, and in vitro and in vivo evaluation methods. The key approaches covered are floating systems, swelling systems, bioadhesive systems, and expandable systems.

1. • APPROACHES
• RELEASE KINETICS
• EVALUATION
GASTRORETENTIVE DRUG
DELIVERY SYSTEM
-MADHURA NEWREKAR
M .Pharm (QA)
1

2. CONTENTS
INTRODUCTION
ANATOMY & PHYSIOLOGY OF STOMACH
FACTORS AFFECTING GRT
GASTRORETENTIVE Vs OTHER CONVENTIONAL DDS
ADVANTAGES & DISADVANTAGES
APPROCHES FOR GI MODULATION
RELEASE KINETICS
EVALUATION
RECENT ADVANCES IN GASTRORETENTIVE DDS
CONCLUSION
2

3. Oral DDS
Advantages:
patient
compliance
Disadvantages:
Fluctuations in
plasma
concentration
Controlled
Release DDS
Advantages:
Predictable plasma
concentration
Disadvantages:
• Unpredictable
gastric emptying
time
• Short gastric
retention time
Site specific , orally
administered ,
prolonged GRT
Gastroretentive DDS
• Improves
bioavailability
• Reduced drug waste
• Increases duration
of drug release
• Local action
3

4. GASTRORETENTIVE DRUG DELIVERY SYSTEM
• It is an approach to prolong
gastric retention of drug.
• To target site specific release
in upper gastrointestinal
tract.
• For local and systemic
effects.
4

5. 5
It is locally effective in treatment of:
 Heartburns
 Infections caused due to Helicobacter pyroli
like peptic ulcer
 Chronic gastritis .
It is systemically effective in treatment :
 Which requires longer duration of drug action.
 Which requires repeated administration of
drug, so to reduce frequent dosing.
 e.g. any infection

6. ANATOMY AND PHYSIOLOGY OF STOMACH
• 3 Parts :
• Fundus, Body ,Antrum Pyrolus
• Fundus and body acts as a
reservoir for undigested food
• Antrum is the main site for mixing
It also acts as a pump by gastric
emptying by propelling actions
6

7. GASTROINTESTINAL MOTILITY AND GASTRIC
EMPTYING
 Gastric emptying occurs during
fasting as well as fed states.
 During the fasting state an inter-
digestive series of electrical events
take place, which cycle both through
stomach and intestine every 2 to 3
hours. They are called as migrating
myoelectric complexes(MMC).
 In the fed state, this cycle is
delayed and hence the gastric
emptying rate is slowed.
MOTILITY PATTERN
7

8. FACTORS AFFECTING GASTRIC RETENTION
TIME
• Density of dosage form : A density of <1.0 gm/cm3 is required
to exhibit floating property.
• Size of the dosage form: The larger size would not allow the
dosage form to quickly pass through the pyloric antrum into the
intestine.
8

9. • Food intake and nature of food: Feeding of polymers of fatty
acid salts leads to decrease in the gastric emptying rate.
• Caloric content: Gastric retention time can be increased
between 4 to 10 hours with a meal that is high in proteins and
fats.
• Frequency of feed: The gastric retention time can increase by
over 400 minutes when successive meals are given compared
with a single meal .
9

10. • Gender: Generally females have slower gastric emptying rates
than male.
• Age: In case of elderly persons, gastric emptying is slowed
down.
• Concomitant drug administration: Anticholinergic like atropine
and propentheline, opiates like codeine and prokinetic agents
like metoclopramide and cisapride will increase gastric emptying
rate.
10

11. GRDDS VS OTHER CONVENTIONAL DDS
Sr.
No.
Parameters Conventional
Drug Delivery
System
Gastroretentive
Drug Delivery
System
1. Toxicity High risk of
toxicity
Low risk of toxicity
2.
Patient
Compliance Less
Improves patient
compliance
3.
Drug with narrow
absorption
window in GIT
Not suitable Suitable
11

12. 4.
Drugs having
shorter half lives
Not much
advantageous
Very much
advantageous
5.
Drugs which are
poorly soluble at an
alkaline pH
Not much
advantageous
Very much
advantageous
12

13. ADVANTAGES
• Sustained drug delivery.
• Enhanced bioavailability.
• Reduced frequency of dosing.
• Reduced fluctuations in drug concentration
• Extended time over critical concentration
• Improved selectivity in receptor activation
• Targeted therapy for local ailments in upper GIT.
• Site specific drug delivery.
13

14. DISADVANTAGES
14
• Floating drug delivery systems require high fluid level in stomach
to float and work effectively.
• In patients with achlorhydria can be questionable in case of
swellable system.
• The mucus on the walls of the stomach is in a state of constant
renewal, resulting in unpredictable adherence.
• Retention of high density systems in the antrum part under the
migrating waves of the stomach is questionable.

15. 15
• Unsuitable for drugs with limited acid solubility. e.g. Phenytoin
• Unsuitable for drugs that are unstable in acidic environment.
e.g. Erythromycin
• Unsuitable for drugs that irritates or causes gastric lesions on
slow release. e.g. Aspirin & NSAID’s
• Unsuitable for drugs that are absorbed selectively in colon. e.g.
corticosteroids.

16. DRUGS SUITABLE FOR GI MODULATION
 Drugs those are locally active in the stomach. e.g. misroprostol,
antacids etc.
 Drugs that have narrow absorption window in gastrointestinal
tract. e.g. levodopa ,furosemide, riboflavin etc.
 Drugs that exhibit low solubility at high pH values. e.g.
diazepam, chlordiazepoxide,verapamil HCl.
16

17. DRUGS UNSUITABLE FOR GI MODULATION
 Drugs that have very limited acid solubility. e.g. phenytoin .
 Drugs that suffer instability in the gastric environment. e.g.
erythromycin .
 Drugs intended for selective release in the colon. e.g. 5- amino
salicylic acid and corticosteroids etc.
17

18. APPROACHES TO GASTRIC RETENTION
APPROACHES
LOW DENSITY
SYSTEMS
NONEFFERVESCENT
SYSTEMS
COLLOIDAL GEL
BARRIER GEL
SYSTEM
MICROPOROUS
COMPARTMENT
SYSTEM
ALGINATE BEADS
HOLLOW
MICROSPHERES
EFFERVESCENT
SYSTEMS
VOLATILE LIQUID
CONTAINING
SYSTES
GAS GENERATING
SYSTEMS
RAFT FORMING
SYSTEM
HIGH DENSITY
SYSTEMS
MUCOADHESIVE
SYSTEMS
SWELLING SYSTEMS
EXPANDABLE
SYSTEM
MAGNETIC
SYSTEM
18

19. LOW DENSITY SYSTEMS (FLOATING SYSTEMS)
• NONEFFERVESCENT SYSTEMS:
• Colloidal gel barrier systems:
• The air trapped in by the swollen polymer maintains a density
less than unity.
19

20. 20
Polymers: Cellulose type , polysaccharides ,matrix forming
polymers .
On coming in contact with gastric fluid, the hydrocolloid in the
system hydrates and forms a colloid gel barrier around its surface.

21. • Microporous compartment system:
• The encapsulation of a drug reservoir inside a microporous
compartment with pores along its top and bottom walls.
• The peripheral walls of the drug reservoir compartment are
completely sealed to prevent any direct contact of gastric
surface with the undissolved drug.
• Gastric fluid enters through the aperture, dissolves the drug and
carries the dissolved drug for continuous transport across the
intestine for absorption.
21

22. • Alginate beads:
 They are prepared by dropping sodium alginate solution into
aqueous solution of calcium chloride, causing the precipitation
of calcium alginate.
 Freeze dried in liquid nitrogen at -4 ͦ C for 24 hours.
 Beads are of spherical size and 2.5 mm in diameter.
22

23. • Hollow microspheres (microballoons):
• Hollow microspheres loaded with drug in their outer polymer
shelf were prepared by a novel emulsion solvent diffusion
method.
• The ethanol/dichloromethane solution of the drug and an
enteric acrylic polymer was poured into an agitated solution of
Poly Vinyl Alcohol (PVA) that was thermally controlled at 40ºC.
23

24. • The gas phase is generated in the dispersed polymer droplet by
the evaporation of dichloromethane formed and internal cavity in
the microsphere of the polymer with drug.
24

25. • EFFEREVESCENT SYSTEMS:
• Volatile liquid containing system:
• These type of systems consist of two chambers separated by an
impermeable, pressure-responsive,movable bladder.
• The first chamber contains the drug and the second chamber
contains the volatile liquid. The device inflates, and the drug is
continuously released from the reservoir into the gastric fluid .
• An inflatable chamber ,which contains a liquid e.g. Ether,
cyclopentane, that gasifies at body temperature to cause the
inflatation of the chamber in the stomach
25

26. 26
• The device may also consist of bio erodible plug made up of
PVA, polyethylene, etc. That gradually dissolve causing the
inflatable chamber to release gas and collapse after a
predetermine time to permit the spontaneous ejection of the
inflatable system from the stomach.

27. • Gas generating systems:
• These delivery systems utilize effervescent reaction between
carbonate/bicarbonate salts and citric/tartaric acid to liberate
CO2, which get s entrapped in the gellified hydrocolloid layer of
the systems, thus decreasing its specific gravity and making it
float over chyme .
• The drug is dispersed in a matrix of swellable polymer.
27

28. HIGH DENSITY SYSTEMS
• High density pellets are small enough to be retained in the
rugae or folds of the stomach body near the pyloric region.
Dense pellets trapped in rugae also tend to withstand the
peristaltic movements of the stomach wall.
• With pellets, the GI transit time can be extended from an
average of 6–25 hours, depending more on density than on
the diameter of the pellets.
• Commonly used excipients are barium sulphate, zinc oxide,
titanium dioxide and iron powder, etc.
• These materials increase density by up to 1.5–2.4g/cm-3.
28

29. BIOADHESIVE / MUCOADHESIVE SYSTEMS
.
• Bioadhesive polymers : polycarbophil, carbopol, lectins,
chitosan and gliadin, etc .
• The mechanism:
1.Hydration mediated adhesion:
Certain hydrophilic polymers have the tendency to imbibe
large amount of water and become sticky.
2.Bonding mediated adhesion:
Physical or mechanical bonds can result from deposition
and inclusion of the adhesive material in the crevices of the
mucusa.
29

30. • Secondary chemical bonds, contributing to bioadhesive
properties, consist of dispersive interactions (i.e. van der Walls
interactions) and stronger specific interaction, which include
hydrogen bonding.
• The hydrophilic functional groups responsible for forming
hydrogen bonds are the hydroxyl (--OH) and the carboxylic
groups (--COOH).
3.Receptor mediated adhesion:
• Certain polymers have the ability to bind to specific receptor
sites on the cell surface. The receptor mediated events serves
as a potential approach in bio/muco- adhesion, hence
enhancing the gastric retention of dosage forms.
30

31. 31
 The wetting theory
Intimate contact with the mucous layers.
 The diffusion theory
Physical entanglement of mucin strands into the flexible polymer
chains.
 The absorption theory
Vander Waal forces and hydrogen bonding.
 The electron theory
Attractive electrostatic forces.

32. SWELLING SYSTEMS
• These are the dosage forms, which after swallowing, swells to an
extent that prevents their exit from the pylorus.
• These systems may be named as ‘plug type systems’, since they
exhibit the tendency to remain logged at the pyloric sphincter if
that exceed a diameter of approximately 12-18mm in their
expanded state.
32

33. 33
• Chitosan, HPMC, sodium Starch glycolate, Carbapol are used.
• The balance between the extent and duration of swelling is
maintained by the degree of cross linking between the polymeric
chains.

34. EXPANDABLE SYSTEMS
• These GRDFs are easily swallowed and reach a significantly
larger size in the stomach due to swelling or unfolding
processes that prolong their GRT.
• After drug release, their dimensions are minimized with
subsequent evacuation from the stomach.
• Gastroretention is enhanced by the combination of substantial
dimensions with high rigidity of the dosage form to withstand the
peristalsis and mechanical contractility of the stomach.
34

35. 35
Expandable systems

36. 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 work, the external
magnet must be positioned with a degree of precision that
might compromise patient compliance.
36

37. COMMONLY USED DRUGS IN FORMULATION OF
GRDDS
37

38. POLYMERS AND OTHER INGRIEDIENTS USED IN
FORMULATION OF GRDDS
38

39. PRODUCTS AVAILABLE IN MARKET
39
Dosage form Drugs Brand name Company,Country
Floating control release
capsule
Levodopa,
Benseramide
MADOPAR Roche products,
USA
Floating capsule Diazepam VALRELEASE Hoffmann Laroche,
USA
Effervescent floating
liquid alginate
preparation
Aluminium hydroxide,
Magnesium carbonate
LIQUID
GAVISCON
Glaxo Smith
Kline,India
Floating liquid alginate
preparation
Aluminium Magnesium
antacid
TOPALKAN Pierre fibre
drug,France
Colloidal gel forming
capsule
Ferrous sulphate CONVIRON Ranbaxy,India
Gas generating floating
swelleble tablets
Ciprofloxacin CIFRAN OD Ranbaxy,India
Mucoadhesive system Furosemide LASIX
RETARD
Sanofi,India

40. RELEASE KINETICS OF GRDDS
40
1. SWELLING SYSTEM:
• Swelling can be described as a second order reaction.
• Considering that the swelling process is affected by specific relations between the molecules
of the swelling medium and the polymer pendant groups (amines, amides, carboxy), one can
expect many kinds of polymer-solution interactions, and probably a complex kinetics.
2. FLOATING SYSTEM:
• The release kinetics will depend on the polymers used and it usually follows zero or first
order kinetics.
3. MUCOADHESIVE SYSTEMS:
• It follows first order kinetics as the rate of drug release is dependent on the concentration of
the drug present.

41. EVALUATION
• IN VITRO EVALUATION:
i) Floating systems
a) Buoyancy Lag Time
It is determined in order to assess the time taken by the dosage form to float on
the top of the dissolution medium, after it is placed in the medium. These
parameters can be measured as a part of the dissolution test.
b) Floating Time
Test for buoyancy is usually performed in SGF Simulated Gastric Fluid
maintained at 370C.The time for which the dosage form continuously floats on
the dissolution media is termed as floating time.
c) Specific Gravity / Density
Density can be determined by the displacement method using Benzene as
displacement medium.
41

42. ii) Swelling systems
a) Swelling Index
After immersion of swelling dosage form into SGF at 370C, dosage form
is removed out at regular interval and dimensional changes are measured
in terms of increase in tablet thickness / diameter with time.
b) Water Uptake :
It is an indirect measurement of swelling property of swellable matrix.
Here dosage form is removed out at regular interval and weight changes
are determined with respect to time. So it is also termed as Weight Gain.
Water uptake = WU = (Wt – Wo) * 100 / Wo
Where, Wt = weight of dosage form at time t Wo = initial weight of dosage
form
42

43. • In vitro dissolution test:
In vitro dissolution test is generally done by using USP apparatus
with paddle and GRDDS is placed normally as for other
conventional tablets.
43

44. IN VIVO EVALUATION
RADIOLOGY SCINTIGRAPHY GASTROSCOPY
MAGNETIC
MARKERS
ULTRASONO
GRAPHY
• 13 C
OCTANOIC
ACID
BREATH
TEST
44

45. RECENT ADVANCES IN GRDDS
45
• Floating Rafts have been used in the treatment of
Gastric esophageal reflux disease (GERD).The
mechanism involved in the raft formation includes the
formation of viscous cohesive gel in contact with
gastric fluids, wherein each portion of the liquid swells
forming a continuous layer called a raft.This raft floats
on gastric fluids because of low bulk density created by
the formation of CO2.
• Usually, the system contains a gel forming agent and
alkaline bicarbonates or carbonates responsible for the
formation of CO2 to make the system less dense and
float on the gastric fluids

46. 46
• Novel adhesive material derived from
fimbriae of bacteria or its synthetic
analogues are also being tried for the
better attachment to the gut.

47. CONCLUSION
• To design a successful GRDF ,it is necessary to take into consideration
1.Physiochemical properties of the drug
2.Physiological events in GIT
3.Formulation strategies
4.Correct combination of drug and excipients.
• GRDD offers various potential advantages for drugs with poor bioavailability.
• GRDDs are the most preferable system in order to deliver the drugs which
have a narrow absorption window near the gastric region..
• Now a lot of research program is going on to develop new concepts.
• In future,the system will become more promising and popular.
47

48. REFERENCES
48
• Yie W Chien , Novel Drug Delivery Systems , 2 nd Edition , Revised and expanded ,Drugs and
Pharmaceutical Sciences , Volume 50 , Page no:164-177.
• N.K.Jain, Progress in Controlled & Novel Drug Delivery System, 1st edition 2004,CBS
Publication, p.no 76-97.
• Amit Kumar Nayak, Ruma Maji and Biswarup Das ,Gastroretentive Drug Delivery System:
A Review ,Asian Journal of Pharmaceutical and Clinical Research,Vol.3, Issue 1, January-
March 2010,1-8.
• S.Gopalakrishnan et al ,Journal of Pharmaceutical Science and Technology ,Vol. 3 ,
2011,548-554.
• Sunil Kumar, Faraz Jamil, Meenu Rajput and Saurabh Sharma ,Gastro Retentive Drug
Delivery System: Features and Facts ,International Journal of Research in
Pharmaceutical and Biomedical Sciences ,Vol. 3 ,Jan – Mar 2012 ,126-135.
• Chhetri et al.,An overview on gastroretention drug delivery system , Journal of science
and technology ,kathmandu university, Vol.10, No.I, November 2014, 90-103.

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