This document discusses gastro-retentive drug delivery systems (GRDDS), which aim to retain dosage forms in the stomach for an extended period of time to slowly release drugs. It describes several approaches for GRDDS, including high density systems, magnetic systems, swellable systems, floating drug delivery systems, and bioadhesive/mucoadhesive systems. The document provides examples of drug candidates suitable for each approach and explains the mechanisms by which they prolong gastric retention times. It also lists some advantages and limitations of GRDDS.

1. Gastro-Retentive Drug Delivery Systems
Presented by – Shubham Patil
M. Pharm 1st Year Pharmaceutics
Roll no. 10
Poona College of Pharmacy, Pune

2. CONTENTS :
 Introduction
 Potential Candidates for GDDS
 Drug Candidates not suitable for GDDS
 Factors affecting the GDDS
 Advantages
 Limitations/Disadvantages
 Approaches to Gastric Retention
 References

3. INTRODUCTION
1)Gastro-retentive drug delivery system (GRDDS) has gained
immense popularity in the field of oral drug delivery recently. It is
a widely employed approach to retain the dosage form in the
stomach for an extended period of time and release the drug
slowly that can address many challenges associated with
conventional oral delivery, including poor bioavailability.
2)Gastro-retensive drug delivery is an approach to prolong gastric
residence time, there by targeting site-specific drugs release in the
upper gastrointestinal tract (GIT) for local or systemic effects.
3)It is obtained by releasing dosages form into stomach and by
releasing in controlled manner.

5. The gastric motility pattern
is systematized in cycles of
activity as well as dormancy.
The duration of each cycle is
90–120 min and it contains
four phases, as mentioned in
Table 1

6. POTENTIAL CANDIDATS FOR GRDDS
 Drugs acting locally in the stomach.
E.g. Antacids and drugs for H. Pylori viz., Misoprolol.
 Drugs that are primarily absorbed in the stomach.
E.g. Amoxicillin
 Drugs that is poorly soluble at alkaline pH.
E.g. Furosemide, Diazepam, Verampil, etc.
 Drugs with a narrow absorption window.
E.g. Cyclosporine, Levodopa, Methotrexate etc.

7. Drugs which are absorbed rapidly from the GI tract.
E.g. Metronidazole, tetracycline.
Drugs that degrade in the colon.
E.g. Ranitidine, Metformin.
Drugs that disturb normal colonic microbes.
E.g. Antibiotics against H. Pylori.
Drugs with less half life

8. DRUG CANDIDATES NOT SUITABLE FOR
GRDDS
 Drugs that have very limited acid solubility.
E.g. Phenytoin, etc.
 Drugs that suffer instability in the gastric environment.
E.g. Erythromycin, etc.
 Drugs intended for selective release in the colon.
E.g. 5-Amino salicylic acid and corticosteroids, etc.
 Drugs having extensive first pass metabolism.

9. FACTORS AFFECTING THE GRDDS
1.Density
2.Size and Shape of the dosage form
3.Single or Multi unit formulation
4.Age
5.Gender
6.Body posture
7.Frequency of intake
8.Diseased state of an individual

10. ADVANTAGES :
1) Enhanced bioavailability
2) Sustained drug delivery/reduced frequency of Dosing
3) Targeted therapy for local ailments in the upper GIT
4) Reduced fluctuations of drug concentration
5) Improved selectivity in receptor activation
6) Reduced counter-activity of the body
7) Extended effective concentration.
8) Minimized adverse activity at the colon.

11. LIMITATIONS/DISADVANTAGES :
1) The drug substances that are unstable in the acidic environment of the
stomach are not suitable candidates to be incorporated in the systems.
2) These systems require a high level of fluid in the stomach for drug delivery
to float and work efficiently.
3) Not suitable for drugs that have solubility or stability problem in GIT.
4) Drugs which are irritant to gastric mucosa are also not suitable.
5) These systems do not offer significant advantages over the conventional
dosage forms for drugs, which are absorbed throughout GIT.

13. APPROACHES TO GASTRIC
RETENSION :
1) High density system
2) Low density system
3) Mucoadhesive system
4) Raft forming system
5) Swellable system
6) Super-porous hydrogels
7) Self unfolding systems

15. A. HIGH DENSITY SYSTEM :
 Different approaches have been adopted by
researchers to enhance gastric residence time with
the prolonged drug release.
 The concept of high density formulation is one such
approach (Fig. 2).
 The developed dosage form was made heavy
(density: 2.5 to 3.0 g/ml) to withstand in vivo
peristaltic movement and remained intact in
spite of the GIT disturbance.
 Accordingly, the GI transit time was expected to prolong for an average of 5.8 h
to 25 h. Barium sulfate, iron powder, titanium oxide, and zinc oxide were
incorporated in the formulation to increase the density of the dosage form.

16. B. MAGNETIC SYSTEM :
Another novel idea was postulated to retain the
dosage form within the stomach by the
application of a magnetic field.
The dosage form would contain magnetically
active elements.
One external magnet was required to position on
the abdomen over the location of the stomach to
retain the administered drug in place (Fig. 3).
Though innovative in design, lack of patient
compliance was one of the major setbacks for in
vivo design of this delivery system.

17. C. SWELLABLE SYSTEM :
With the introduction of swelling and expanding
system (Fig. 4), GRDDS managed to achieve significant
success both in vitro and in vivo in order to retain the
dosage form in the stomach .
Bolton and Desai reported one such system that was
designed to increase in size bigger than the diameter
of pyloric sphincter and remain logged there (Fig. 4).
Alternatively, the system was named as ‘plug type
systems’ due to their pyloric sphincter blocking
attribute.
Once the polymer came in contact with the gastric
fluid, it absorbed water and swelled.
 The selection of a suitable polymer (or combination of polymers) with an
appropriate molecular weight/viscosity grade and swelling properties enabled
the dosage form to attain sustained-release characteristic.

18. D. FLOATING DRUG DELIVERY SYSTEM :
Floating drug delivery systems have a bulk density
lower than gastric fluids and thus remain buoyant in
the stomach for prolonged period of time without
affecting the gastric emptying rate.
While the system is floating on the gastric contents,
the drug is released slowly at a desired rate from the
system.
This type is also called as hydro dynamically
balanced system (HBS).
Various effervescent components (e.g. sodium
bicarbonate, tartaric acid and citric acid) were mixed
within the dosage form.
When these components come in contact with the gastric contents, carbon
dioxide (CO2) is liberated as a result of a chemical reaction it swells and
float on the surface.

19. E. BIOADHESIVE OR MUCOADHESIVE SYSTEM :
Bio-adhesive or muco-adhesive drug delivery
systems were also tried as gastro-retentive systems.
The dosage form was made to be attached inside
the lumen of the stomach wall and survive the
gastrointestinal motility for a longer period (Fig. 6).
It was also beneficial as a site specific design to
promote local drug absorption in an infected area of
the stomach.
Muco-adhesive excipients like polycarbophil,
lectins, Carbopol, chitosan, carboxymethylcellulose
(CMC), pectin and gliadin were reported as
formulation compositions for this kind of design .
The combination of macho-adhesion and floating or swelling mechanism is being
adopted as another novel approach for improved gastro-retention attributes.

20. The basis of adhesion in that a dosage form can stick to the mucosal
surface by different mechanism. These mechanism are :
1. The wetting theory.
2. The diffusion theory.
3. The absorption theory.
4. The electron theory.

25. References :
1. Review Article
Gastro-retentive drug delivery systems and their in vivo success: A recent update
Uttam Kumar Mandal , Bappaditya Chatterjee, Faria Gias Senjoti
Link :
https://drive.google.com/file/d/1HQRDYz71BmgNftqkiPcwLlPIdexzG3Ub/view?usp=
sharing
2. US Patent
Bolton & Desai
Link :
https://drive.google.com/file/d/162il2U2Bb5_aMnPJbh2vLKKC1T3PFvM0/view?usp=
sharing

26. 3. S.P.Vyas, Roop K. Khar,
CONTROLLED DRUG DELIVERY – Concepts & Advances,
Vallabh Prakashan,
pp – 196-217.
4. N.K. jain,
Progress in controlled & Novel Drug Delivery System,
1st edition 2004 CBS
Publishers, pp – 76-97.
References :