Gastro retention drugs

1. welcome
to
Wonder worlds

2. Gastro-retentive drug
delivery system
Submitted By
Pandhari Vithoba ingle
B. Pharm final yr. (7th sem
Guded by
MR. Amol G. Jadhao
(M.Pharm, Ph. D.Pursuing)
(Assit. prof. of pharmaceutics department)

3. INTRODUCTION
Ganstroretention drug delivery in a newly discover erred drug delivery system main approach of this
delivery is to prolong the drugs gastric resid ence time, thus Targeting site- specific drug release in the
upper GIT for local or systemin effects.
1) High Density(sinking)system: In this system, the drug is retained in the bottom of the stomach.
2) Low Density (Footing) System: This system causes buoyancy in gastric fluid.
3) Mucoadhesive System : This system causes bioadhesion of the drugs to stomach mucosa.
4) Unfordable, Extendible, or Swellable System: This system limits emptying of the dosage forms through the
pyloric sphincter of stomach.
5) Superporous Hydrogel System And Magnetic system: These are some other examples of GRDDS.

4. ADVANTAGES
1) It increases the bioavailability and curative efficiency of drugs.
2) It increases the economic usage of dosage.
3) It reduces the risk of antibiotic resistance by stabiles ing therapeutic levels over prolonged
period by removing fluctuations.
4) It increases the efficiency of drug release in case of short half-life drugs.
5) It causes flip-flop of pharmacokinetics.
6) It provides a narrow curative index.
7) It reduces any fluctuations in drug concentration and their effects.
8) It is a highly efficient system due to reduced counter activity by the baby.
9) It provides controlled rates of fluctuation thus a wider array is provided for selectivity in
receptor activation.
10) Being a systemic and controlled drug delivery system, it reduces the checks of drug over-
exposure at the diseased site.
11) It is u Sed to tret problems related to stomach and small intestine as the system sustains the
drug release, thus inscribes the gastric residence time and provides local therapy on these
organs.

5. disadvantages
1) It increases the level of fluids required in the stomach.
2) It is not suitable for drug having low solubility in gastric fluid, causing gastrointestinal
irritation, inflection in acidic environment, and meant for selection release in the colon.
3) In such a system, adherence of drugs with the mucus cannot be predicted due to the
continuous renewal of mucus wall of stomach.
4) GRDDS is fed into the system after the meal; the drugs residence time in stomach depends on
digestive stets of the subject.
5) The drugs residence time in stomachs depends on the subj etc being positioned upright.
6) Drugs which are formulated as hydrogel-based swelling system takes longer time to swell.

6. Floating Drug Delivery System
EFFERVESCENT
SYSTEM
NON-
EFFERVACENT
SYSTEM
1. Gas- generating system:
2. Single layer floating
tablet
3. Multiple unit type pills
4. Bilayer floating tablet
5. Floating system with
ion exchange resin
2) Volatile liquid containing system
I) Intragastric
gastrointestinal
II) Inflatable
gastrointestinal
1) Expandable and
Swellable systems
2)Inherently low density
system
 Classification of floating drug delivery system

7. application
1) FOLLOWINGARETHEAPPLICATIONSOFTHEGRDDS:
2) Enhanced Bioavailability: Riboflavin Gastroretentive Dos age From (GRDF) shows enhanced
bioavailability as compared to the non-GRDP polymeric formulations. Many other processes,
related to drug absorption and transit in the GIT, act concurrently to influence the drug
absorption rate,
3) Sustained Drug Delivery/Reduced Frequency of Dosing: Drugs having short biological half-
life, and sustained and slow input from GRDF enhance the pharmacokinetic factors and
decrease the dosing frequency. This property increases patient compliance, and thus improves
therapy.
4) Targeted Therapy for Local Ailments in the Upper GIT: Local therapy can be exerted
on stomach and small intestine with prolonged and sustained administration of the drug from
GRDF to the stomach. Such targeted therapy helps to achieve the therapeutic drug
concentrations locally; while, minimal systemic concentrations are achieved after drug
absorption and distribution.
5) Reduced Fluctuations of Drug Concentration: By continuous intake of the drug following
GRDF administration, blood-drug concentrations can be maintained within a narrower range
as compared to the immediate release dosage forms. This minimises the fluctuations in drug
effects and prevents the adverse effects caused due to higher concentration.
6) Site Specific Drug Delivery: Drugs having limited absorption sites in upper small intestine
can be formulated as a floating dosage form. Controlled and slow delivery of drug to the
stomach provides local therapeutic levels and also limits the systemic exposure to the drug.
This apron ach also dec

8. FactorsAffectingGastricRetentionTimeoftheDosageFormFollowingfactorsaffectthegastricretentiontimeof thedosage
form
1) Density: Dosage form should have a less density than that of the gastric contents
(1.004g/ml).
2) Size: Dosage form with a diameter of more than 7.5mm show more gastric residence
time as compared to the dosage form having 9.9mm diameter.
3) Shape of the Dosage Form: The tetrahedron-shaped dosage form remains for a longer
period in the stomach than other devices of similar size. More predictable release profile
is observed for single or multiple unit formulation, along with insignificantly impaired
performance due to failure of the units.
4) As compared to single unit dosage form, multiple unit formulations allow co-
administration of u nits with different release profile or showing incompatibility with
gastric substances and have a large safety margin against dosage form failure.
5) Fed or Unfed State: During fasting the gastrointestinal motility shows periods of strong
motor activity at intervals of 1.5-2 hours. The Migrating Motor Complex (MMC) allows
passing of undigested food material from the stomach and if the timing of the
formulation coincides with that of MMC, the GRT of the unit can be very short, but,
MMC is delayed and GRT is longer during fasting
6) Nature of Meal: The motility pattern of the stomach changes to a fed state due to intake
of indigestible polymers or fatty acids. This reduces the gastric empty ing rate and
prolongs the drug release.
7) Caloric Content: Due to intake of high caloric food (such as protein and fat), GRT can
be increased by 4-10 times.
8) Frequency of Feed: If successive meals are given, the GRT can be increased over 400
minutes in comparison to the single meal due to low frequency of MMC.
9) Gender: Mean ambulatory GRT in males (3.4 hours) is less er than that of females (4.6
hours) of the same age and race, irrespective of height, weight, and body surface.
10) Age: Significantly longer GRT is observed in people of more than 70 years of age.
11) Concomitant Drug Administr ation: Anticholinergic drugs (eg, atropineand
propantheline) and opiates (e.g., codeine) can extend the GRT

9. Effervescent System
In effervescent systems, gas -generating agents, carbonates ( e.g.,
sodium bicarbonate), and other organic acids (e.g., citric acid and
tartaric acid) are used to produce carbon dioxide (C*O_{2}) gas. This
decreases the density of system and allows it to float on the gastric
fluid. An alternative of this systeminvolvesincorporating matrix-
containing portion of liquid, which produces a gas that evaporates at
body temperature.

10. Effervescent systems are further categorised into the following
two types:
1) Effervescent/Gas-Generating System: This system generates
gas bubbles to achieve floatability or buoyancy. Such a buoyant
system uses matrices made-up of swellable polymers, such as
polysaccharides (e.g., chitosan), and effervescent components
e.g., sodium bicarbonate, citric acid or tartaric acid).The optimal
stoichiometric ratio of citric acid and sodium bicarbonate for gas
generation should be 0.76: 1. In gas-generating system, carbon
dioxide is released and the formulations tarts floating in the
stomach

11. Low Density or Floating Drug Delivery System A careful gastric retention can achieve optimum level of drug
bioavailability, and
floating drug delivery system is a novel approach used for the same purpose. Drugs that
undergo absorption in the stomach or upper small intestine formulated in this system. This
method has no effect on the rate of gastric emptying over a prolonged time. Since the
density of floating drug delivery system is lower than that of gastric fluid, the drugs remain
buoyant in the stomach and are released slowly. In stomach, the emptying of residual
system is followed by the drug release. This increases the gastric retention time and
controls the fluctuations in plasma drug concentration. Following are the pre-
requisites for floating drug delivery system:
1) It requires a reservoir for slow content release.
2) It should be maintained at a s pecific gravity lower than that of gastric contents (1.004-
1.01gm/cm³)
3) It should form a cohesive gel barrier.

12. Mechanism of Floating Drug Delivery System
Siow release of drug is accompanied with the required rate
during the system flow on the gastric contents. Release of
drug is followed by removal of the residual system from the
stomach. However, minimum levels of gastric contents and
an appropriate level of floating force (F) are required to
achieve buoyancy retention principle and to keep the
dosage form buoyant over meal surface

13. High Density (Sinking) or Non Delivery System -Floating Drug
In high density or non-floating drug delivery system, dosage forms having density
more than that of the normal stomach content (~1.004gm/cm 3) are formulated.
Such formulations are prepared by coating the drug on a heavy core or by mixing
the drug with inert materials (like iron powder er, barium sulphate, zinc oxide,
titanium oxide, etc.). These materials increase the density by up to 15-24ga/cm². A
density of about 2.5 gm/cm² is essential for significant prolongation of gastric
residence time, But, this system is not effect humans, and thus such dosage form are
not marketed

14. Super-Porous Hydrogel System
The super-porous hydrogel system is different from the conventional type
system to warrant separate classification. This system involve s improvement
of the gastric retention time of super porous hydrogels of average pore size
>100 µm. The super-porous hydrogels swell to equilibrium size within 60
seconds due to rapid water uptake by capillary wetting through numerous
interconnected open pores. The super-porous hydrogels swell to a large size
(swelling ratio: 100 or more) and gain sufficient mechanical stern goths to
withstand pressure by gastric contraction. The super-porous hydrogel system is
used to formulate hydrophilic particulate materials.

15. Magnetic System
The magnetic system is used to increase the gastric retention time. It is based on the
principle that the dosage form contains a small internal magnet, and a magnet placed on
the abdomen over the position of stomach. Although it has been observed that magnetic
system works, the external magnet should be placed with a degree of precision that might
compromise patient compliance

16. Non-Effervescent System
1. The non-effervescent floating drug delivery system works on the mechanism
of
2. swelling of polymer or bioadhesion to mucosal layer in GIT. This system
utilises
3. gel-forming or highly swellable cellulose tyre hydrocolloids, hydrophilic
gums,
4. polysaccharides, and matrix-forming materials (e.g., polycarbonate,
polyacrylate,
5. polymethacrylate, polystyrene), and bioadhesive polymers (e.g., chitosan) as
the
most common excipients.
The non-effervescent system is of the following types:

17. Expandable or Swellable System:
1) If the dosage form is bigger than the
2) pyloric sphincter, it will withstand gastric transit in the stomach. But the
3) dosage form should be small enough to be swallowed, and should not cause
4) gastric obstruction, either alone or by accumulation. Therefore, expandable or
swellable system (figure 7.10) is formulated such to prolong the gastric
retention time:
1) A small configuration for oral intake,
1) An expanded Gastroretentive form, and
iii) A final small form that enables evacuation after drug release from the

18. Bioadhesive or Mucoadhesive or Gast Ro adhesive Drug Delivery System
In gastropathies drug delivery syst em, a mucoadhesive polymer is used that
adheres to the gastric mucosal surface and prolong its gastric retention time in
the GIT. The property of mucoadhesive polymers to adhere to the mucus layer
makes them very useful excipients in GRRDS. Mucoadhesive polymers can
be of natural origin (e.g., sodium alginate, gelatine, guar gym, etc.) or of
semi-synthetic (e.g. HPMC, Carbopol, sodium carboxymethyl cellulose).
polymers can be cationic, anionic, or neutral. Mucoadhesive

19. 1)Hydration-Mediated Adhesion:
Some hydrophilic polymers acquire
bioadhesive properties by imbibing a large amount of water and becoming
sticky. By controlling the dissolution rate of the polymers, the prolonged
gastroretention of the bio/muco-adhesive delivery system can he controlled.
2) Bonding-Mediated Adhesion:
In this type of adhesion, polymers adhere to
mucus/epithelial cell surface
through various bonding mechation
Deposition and inclusion of the adhesive material in the crevices of muons
may form physical or mechanical 1 bonds. Secondary chemical bonds, that

20. THANK YOU