gastro retentive drug delivery system topic include 1. introduction 2.advantages 3.technology 4.evaluation 5.disadvantages 6. matrix tablet and other relative information regarding the topic

1. Gastro-retentive drug delivery system
Ravish Yadav

2. Content
 Introduction
 Advantages
 Gastro-retentive technologies
 Evaluation of GRDDS
 Disadvantages
 References

3. Introduction
Conventional oral drug delivery system (DDS) is complicated by limited
gastric residence time (GRT).
Rapid GI transit can prevent complete drug release in absorption zone &
reduce the efficacy of the administered dose since the majority of drugs
are absorbed in stomach or the upper part of small intestine.

4. To overcome these limitations, various approaches have been proposed
to increase gastric residence of drug delivery systems in the upper part of
GIT includes gastro retentive drug delivery system (GRDDS).
Among the GRDDS, floating drug delivery system (FDDS) have been
the most commonly used.

5.  Gastro-retentive delivery is one of the site specific delivery of the
drugs at stomach. It is obtained by retaining dosage form into
stomach and drug is being released at sustained manner to specific
site either in stomach or intestine.
What is GRDDS??????

6. Differ from Conventional Release…
Conventional Release GRDDS
Absorption
window

7. Delivery of drugs with narrow absorption window
in the small intestine region.
Longer residence time in the stomach could be
advantageous for local action in stomach, for
example treatment of peptic ulcer disease.
Bio-availability can be improved.
Advantages…

8.  Reduced Frequency of Dosing with improved patient compliance
 Minimize the Fluctuation of drug concentrations
 Site specific drug delivery
 Enhances the Pharmacological effects

9. LIMITATIONS
They require a sufficiently high level of fluids in the
stomach for the drug delivery buoyancy, to float therein and
to work efficiently.
Floating systems are not feasible for those drugs that have
solubility or stability problems in gastric fluid.
Drugs which are well absorbed along the entire GI tract and
which undergoes significant first- pass metabolism, may not
be desirable candidates for GRDDS since the slow gastric
emptying may lead to reduced systemic bioavailability.
Drugs that are irritant to gastric mucosa are not suitable for
GRDDS.

10. Gastric emptying
The process of gastric emptying occurs both during fasting and fed state.
 In fasted state,
• the process of gastric emptying is characterized by an inter digestive
motility pattern that is commonly called migrating motor complex
(MMC)(migrating myloelectric cycle)
• This is a series of events
that cycle through the
stomach and small
intestine every
1.2 to 2hrs.

11. In fed state,
• the gastric emptying rate slowed down because the onset of
Migration Motor Complex (MMC) is delayed
• the feeding state results in a lag time prior to the onset of gastric
emptying
• It is thought that the sieving efficiency of the stomach is enhanced
by the fed pattern or by the presence of food.

12. Salient Features Of Upper Gastrointestinal
Tract
Length
(m)
Transit time
(hr)
pH Absorbing
surface
area (m2)
Absorption
pathway
Stomach 0.2 Variable 1-4 0.1 P,C,A
Small Intestine
6-10 3±1 5-7.5 120-200
P,C,A
F,I,E,CM
P – Passive diffusion C – Aqueous channel transport
A – Active transport F – Facilitated transport
I – Ion-pair transport E – Entero-or pinocytosis
CM – Carrier mediated transport

13. FACTORS CONTROLLING THE GASTRIC
RETENTION TIME OF DOSAGE FORM
1.Density: GRT is a function of dosage form buoyancy.
2. Size
3. Shape of dosage form:Tetrahedron and ring shaped devices.
4. Fed or unfed state:If the timing of administration of the formulation
coincides with MMC, the GRT of the unit can be expected to be very
short. However, in the fed state, MMC is delayed and GRT is
considerably longer.
5. Caloric content:GRT can be increased by 4 to 10 hours with a meal
that is high in proteins and fats.

14. 6. Frequency of feed: The GRT can increase by over 400 minutes,
when successive meals are given compared with a single meal
due to the low frequency of MMC.
7. Gender: Mean ambulatory GRT in males (3.4±0.6 hours) is less
compared with their age and race matched female counterparts
(4.6±1.2 hours), regardless of the weight, height and body
surface.
8. Age: Elderly people, especially those over 70, have a significantly
longer GRT.
9. Posture: GRT can vary between supine and upright ambulatory
states of the patient.

15. Candidates for GRDDS
Drugs acting locally in the stomach E.g. Antacids
Drugs that are principally absorbed in the stomach
Drugs that are poorly soluble at the alkaline pH
Drugs with a narrow window of absorption E.g.
Furosemide
Drugs absorbed readily from the GI tract
Drugs that degrade in the colon
 Drugs with variable Bioavailability
 Drugs with less half life

16. Approaches
STOMACH
Esophagus
Cardia
Body
Pyloric
Sphinctor
Duodenum
Fundus
Pylorus
Pyloric Antrum
1
2
43
1- Floating System
2- Bioadhesive System
3- Swellable System
4- High Density System

17. Classification of
gastro retentive drug delivery systems.

18. Swellable System
Also called ‘ PLUG SYSTEM’
Size of the formulation more
than Pyloric sphincter
It should expand for gastric
retention Should be
Collapsed after lag time

19. High degree of
Cross-linking
Low degree of
Cross-linking
Gastric Fluid
Time

20. Picture of tablet in Dry and Wetted state

21. Disadvantages of Swelling System
 The Dosage form must maintain a size larger than pyloric sphincter
 The Dosage form must resist premature gastric emptying

22. Bio/Muco Adhesive System
Here, the drug is incorporated with bio/
Muco-adhesive agents, enabling the
Device to adhere to the stomach walls,
Thus resisting gastric emptying.
However, the mucus on the walls of
the Stomach is in a state of constant
renewal, Resulting in unpredictable
adherence.
Thus, this approach is not widely used.

23. Bio/Muco Adhesive Polymers
Chitosan
Polyacrylic acid
Carbopol 934P, 971P, 980
Sodium alginate
HPMC K4M, K15M, K100M
Hydroxypropylcellulose (HPC)
Cholestyramine

24. Problem of Muco-adhesive System
Rapid removal of mucus.
We are not sure weather the DF will adhere to the mucus or epithelial
cell layer
DF may adhere to esophagus resulting in drug induced injuries

25. High Density Approach
Density should be more then
stomach content i.e. 3 g/cm3
Capable to withstand with
peristaltic movement of
stomach
Prepared by coating or mixing
drug with heavy inert material

26. Diluents such as…
 barium sulphate (density = 4.9),
 zinc oxide,
 titanium dioxide,
 iron powder
must be used to manufacture such high-
density formulations.

27. Problem with High Density
Approach
 Higher amount of drug require
The dosage form must stand with peristaltic movement of stomach

28. Low Density Approach
(Floating Drug Delivery)
 Retained in stomach
 Useful for poorly water soluble OR
unstable in intestinal Fluid
 Bulk density : Less than gastric fluid, so
remain buoyant in the stomach without
affecting gastric emptying rate for
prolonged period of time
 So drug release slowly at the desired rate
from system

29. Advantages of Low Density Approach
OR
Floating Drug Delivery
Drugs those are...
 Primarily absorbed in the stomach
 Poorly soluble at an alkaline pH
 Narrow window of absorption
 Degrade in colon

30.  When there is a vigorous intestinal movement and a short transit time as
might occur in certain type of diarrhoea, poor absorption is expected.
Under such circumstances it may be advantageous to keep the drug in
floating condition in stomach to get a relatively better response.

31. Disadvantages of Low Density Approach
OR
Floating Drug Delivery
 Not feasible for those drugs that have solubility OR stability problem in
GIT
Require high level of fluid in stomach
 The drugs that may irritate the stomach lining OR are unstable in acidic
environment
 The dosage form should be administered with a full glass of water (200-
250 ml)

32. Classification:
• Noneffervescent systems
1. Single-unit floating dosage system
2. Multiple unit floating dosage system
• Effervescent (gas-generating) systems
1. Single-unit floating dosage system
2. Multiple unit floating dosage system
• Raft-forming systems

33. Non effervescent Systems
Single unit
1. Floating tablets(MATRIX TABLET)
2. Floating capsules(HBS capsules)
3. Tablets with hollow cylinder
4. Microporous reservior
5. Multilayer flexible film

34. 1.MATRIX TABLET
• Incorporating gel forming hydrocolloids HPMC, which is the most
commonly used polymer for floating.
• Out of various grades of HPMC, low viscosity grade are used for
floating purpose.
• Mixture of alginate and HPMC also prepared for floating tablet.

35. Single Layer Tablet Bilayer Tablet
Loading Dose

36. 2.Floating capsules:
HBS Capsules:
 It is Hydrodynamically Balanced System. It is a hard gelatin
capsule containing drug with high level of one or more highly
swellable gel forming hydrocolloids (20-75%) like HPMC, HPC,
HEC, Na-CMC etc.
 When coming in contact with water, the hydrocolloids at the
surface of the system swell and facilitate floating.
• Gel structure controls rate of diffusion of fluid-in and drug- out
making “Receding Boundary”.
• After exterior surface dissolves/erodes, the immediate adjacent
hydrocolloid layer is hydrated and process continues to give
floating for extended period of time.

37. 1. hbs capsules

38. 3.TABLETS IN
CYLINDER
A I R
polypropylene
The device consisting of
two drug-loaded HPMC
matrix tablets, which are
placed within an
impermeable, hollow
polypropylene cylinder (open
at both ends). Each matrix
tablet closed one of the
cylinder’s ends so that an air-
filled space was created in
between, providing a low
total system density. The
device remained floating
until at least one of the
tablets is dissolved.
HPMC matrix
tablet
HPMC matrix
tablet

39. 4.MICROPOROUS
RESERVIOR • Drug reservoir encapsulated
in microporous compartment
having pores on its top and
bottom walls
• Peripheral walls are sealed,to
prevent direct contact with
gastric fluid
• A floating chamber was
attached at one surface
which gives buoyancy to
entire device. Drug slowly
dissolves out via micro pores

40. 5.Multi-layer flexible film:
The device consist of two films which are sealed together
along their periphery and in such a way as to entrap some air
between two films and so make air pocket which imparts
buoyancy.

41. Multiple unit:
• Reduce the inter subject variability in absorption
• Lower the probability of dose dumping.
• Available as
• Beads,
• Micro-spheres,
• Micro-balloons,
• Carrier system.

42. A. Beads
1.CALCIUM ALGINATE/PECTINATE BEADS
2.ALGINATE BEADS with AIR COMPARTMENT
3.OIL ENTRAPPED GEL BEADS
4.CASEIN – GELATIN BEADS

43. 1.CALCIUM ALGINATE/PECTINATE BEADS
Sodium
Alginate
Solution
Dropped to
Calcium
Chloride
Solution
Spherical
Gel
Beads(2.5m
m)
Separate,
Freeze Dried
(-40oC)
24hrs
IONOTROPIC GELATION METHOD
Calcium Pectinate Gel Beads
Calcium-Alginate-Pectinate Gel beads(fasten drug release)
Calcium Alginate + Chitosan Gel Beads(air entrapement
gives Better buoyancy)
porous beads with about 12 hrs buoyancy period &
residence time of 5.5 hrs

44. 2.ALGINATE BEADS with AIR COMPARTMENT
Alginate Bead
in Solution,
before Drying
Coating
before Drying
After Drying
Shrinkage of Bead
During the preparation of calcium alginate beads before drying
process the beads are coated with the coating solution which may be
calcium alginate or mixture of calcium alginate and PVA(water soluble
additive in coating composition which increase membrane
permeability), and then they are dried

45. 3.OIL ENTRAPPED GEL BEADS
Oil – Light weight and Hydrophobic
Pectin has some Emulsification property
Aqueous
Solution of
Pectin
homogenization
Emulsion
Edible
Veg. OIL
extruded to Calcium
Chloride
Solution

47. 4.CASEIN – GELATIN BEADS
• Casein has Emulsification property- Entraps Air Bubbles
• Biodegradable beads
Casein Gelatin
Solution (60oC)
Rapidly stirred
Emulsion
Preheated
Mineral Oil
Rapid
Cooling
(5co )
Add to
Cooled
Acetone
Separated
and
Dried
At Reduced Pressure – NO AIR – Non Floating Beads

48. B.HOLLOW MICROSPHERE
Or MICROBALLOON
Emulsion-solvent diffusion method
• Agitate solution of PVA and thermally control at 40 degree Celsius.
• Ethanol-dichloromethane solution of drug and polymer was poured
into it.
Polymers such as polycarbonate and cellulose acetate were used in the
preparation of hollow microspheres.

49. Mechanism of drug release:
When microspheres come in contact with gastric fluid
the polymer forms a colloidal gel barrier that controls
the rate of fluid penetration into the device and
consequent drug release.

50. d) Carrier systems
CALCIUM SILICATE AS FLOATING CARRIER
Highly Porous
Large Pore Volume
Low Inherent Density
• Granules of calcium silicate as a floating
carrier, which has a characteristically porous
structure .
• Air trapped in the pores of calcium silicate when
they were coated with polymer(HPC).

51. Effervescent systems:
• Gas generating system
• Matrix tablets
• Single layer tablets
• Bilayer tablets
• Multi unit floating pills
• Floating based on ion exchange resin
• Volatile liquid containing system
• Deformable unit with inflatable chamber
• Osmotically controlled DDS

52. 1.Gas generating system
Effervescent reaction between carbonate/ bicarbonate salts and
citric/tartaric acid to liberate CO2,which get enrtapped in the
gellified hydrocolloid layer of the system,decreasing its bulk density
and making it float over chyme.
Matrix tablets:
• Single layer:
CO2 generating components intimately mixed within tablet
matrix.(HPMC,Chitosan,alginate)
• Bilayer tablets:
Gas generating components comprssed in one hydrocolloid
containing layer and drug in other formulated for SR.

53. FLOATING PILLS
DRUG
NaHCO3
Tartaric Acid
Swellable Polymer
(PVA and shellac)

54. ION EXCHANGE RESIN BEADS
Resin
HCO3
HCO3
HCO3
H+ Cl
H+ Cl
H+ Cl
H+ Cl
H+ Cl
Uncoated Beads – No Floating – Escape of CO2

55. This system consists of mainly
two different part attached with
each other, one is floating part
and other is osmotic controlled
part
Floating part made up of
deformable polymeric bag
containing liquid that gasify at
body temperature.Osmotic
pressure controlling part consists
of two part, drug reservoir &
osmotically active compartment.
1.Osmotically controlled DDS
Volatile liquid containing system:

56. 2.Deformable unit with inflatable chamber
These type of systems consist of two chambers separated by
an impermeable, pressure-responsive,movable bladder.
• The first chamber contains the drug impregnated polymeric matrix
• and the second chamber contains the volatile liquid(ether).
• Both enclosed in gelatin shell.
The device inflates, and the drug is continuously released from
the reservoir into the gastric fluid.

57. • Raft-Forming Systems
• This system is used for delivery of antacids and drug delivery
for treatment of gastrointestinal infections and disorders.
• These are liquid preparations having gel forming agent(alginic
acid),Na-bicarbonates and drug, which forms foaming Na-alginate gel,
while reacting with gastric acids.
• This raft floats in gastric fluids because of the low bulk density
created by the formation of CO2
• The raft has pH value higher than that of stomach contents so that in
gastric reflux the wall of oesophagus is not subjected to irritation by
HCl.

58. Evaluation of GRDDS
GRDDS
Hardness Friability
Drug
Content
Diameter
Weight
Variation

59. Evaluation of GRDDS
 Dissolution
medium : 0.1 N HCl
 Temp. : 37 ± 0.5°C
 RPM : 50-100
 Sample analysis :
UV
 Dissolution Study

60. Evaluation of GRDDS
 In-vitro Mucoadhesion
 Apparatus : USP type VI (rotating
cylinder apparatus)
 Medium : 0.1 N HCl
 Temp. : 37 ± 0.5°C
 RPM : 100

61. Evaluation of GRDDS
 Lag time :
 Measurement : 0.1 N HCl at pH 1.2
 Temp. : 37 ± 0.5°C
 Apparatus : USP Type II dissolution apparatus
 A tablet is placed in a beaker containing 100 – 200 ml dissolution
medium & the time for a tablet to emerge on to the surface of the
dissolution medium is known as lag time .

62. Evaluation of GRDDS
 Floating Time
 After achieving lag time, the time taken for a
tablet to remain float on the surface of the
dissolution medium is called floating time.

63. Evaluation of GRDDS
 Water uptake :
 Apparatus : USP type II dissolution apparatus
 Medium : Water
 Temp. : 37 ± 0.5°C
 RPM : 50
WU (%) = Wt. of swollen tab. – Initial wt. of tab. Initial wt.
of tab. × 100

64. Evaluation of GRDDS
 In vitro Mucoadhesive strength

65. Limitation of GRDDS
 It is not recommended for drugs which are unstable at gastric/acidic
pH, insoluble or very low soluble drugs and drugs which causes
gastric irritation.
 For floating, high level of fluid is required in GIT. Also sleeping
condition is favorable for the better results of GRDDS.

66. Limitation of GRDDS
 Bioadhesive systems, cannot prevail longer due to
high turn-over rate of mucus layer and presence of
soluble mucin
For swelling systems, it is necessary that the
formulation should not exit before the appropriate
swelling
 For High density systems, High amount of drug is
require

67. References
• Doshi S.M., Tank H.M., Gastro Retention – An Innovation
over Conventional poorly Soluble Drugs : A review,
International Journal of Pharmaceutical and chemcal
Sciences, 2012;1(2):859-866.
• S. P. Vyas, Roop K. Khar, CONTROLLED DRUG
DELIVERY – Concepts & Advances, Vallabh Prakashan,
page no. 196-217.
• N. K. Jain, Progress in Controlled & Novel Drug Delivery
Systems, 1st edition 2004, CBS Publishers, page no.76-97
• G. Chawla, P. Gupta, V. Koradia, A. K. Bansal,
Pharmaceutical Technology July 2003, 50-68