2. CONTENTS:
1. Introduction
Gastroretentive Drug Delivery SystemGRDDS
Drug Candidates for GRDDS
Approaches to GRDDS
2. Floating Systems
Classification of FDDS
Advantages of FDDS
Disadvantages of FDDS
3. Some articles and researches
3. 1. INTRODUCTION
The ultimate goal of any drug delivery system is:
effective disease/disorder management,
minimum side effects and greater patient
compliance in the cost effective manner.
4. 1. INTRODUCTION
Drug absorption from the gastrointestinal tract is
a complex procedure and is subject to many
variables.
It is widely acknowledged that the extent of
gastrointestinal tract drug absorption is related to
contact time with the small intestinal mucosa
(Hirtz, 1985).
small intestinal transit time is an important
parameter for drugs that are incompletely
absorbed.
5.
6. 1.2. GASTRORETENTIVE DRUG DELIVERY
SYSTEMS
Gastroretentive systems can remain in the
gastric region for several hours
and hence significantly
the gastric residence time of drugs.
Prolonged gastric retention improves
bioavailability, drug waste, and improves
solubility for drugs that are less soluble in a high
pH environment.
7. 1.2.2. DRUG CANDIDATES FOR GASTRIC
RETENTION
i. Acting locally in the stomach (e.g. antibiotics
against H.Pylori, antacids and misoprostol)
ii. Absorbed incompletely due to a relatively narrow
window of absorption in the GIT, such as
cyclosporin, ciprofloxacin, furosemide, L-DOPA,
p-aminobenzoic acid and riboflavin
iii. Unstable in the intestinal or colonic environment
such as captopril or
iv. Exhibit low solubility at high pH values such as
verapamil HCl, diazepam and chlordiazepoxide .
8. 1-drugs that may cause gastric lesions, e.g., non-
steroidal anti-inflammatory agents and
2-drug substances that are unstable in the strong
acidic environment of the stomach, e.g.,erythromycin.
1.2.2. DRUG NOT CANDIDATES FOR
GASTRIC RETENTION
10. 1.2.3. APPROACHES TO GASTRIC RETENTION
A) High density approach
coated pellets, coating drug on a heavy core or mixed with
inert materials such as iron powder, barium sulphate, zinc
oxide and titanium oxide etc..
Recently, a novel famotidine gastric resident osmotic pump
tablet using iron powder as a gas formation and density
increasing agent.
11. B) Low density approach ( Floating systems )
density of pellets should be than 1 g/ml, so as to float
the pellets or tablets in the gastric fluid and, release the
drug slowly for a longer period of time. This type is also
called as Hydro dynamically Balanced System (HBS).
1.2.3. APPROACHES TO GASTRIC RETENTION
13. Floating drug delivery systems are classified depending
up on the two formulations variables:
Effervescent and Non effervescent systems.
Floating systems can be based on several
principles including:
1. gas generation systems (effervescent systems),
2.swelling systems (non effervescent systems), and
3. inherent low density.
2.1. CLASSIFICATION OF FDDS
14. 1. Gas generation systems (effervescent
systems),
matrices prepared using:
1. Swellable polymers such as MC, HPMC.
2. Polysaccharides such as chitosan.
3. Effervescent components such as sodium
bicarbonate, Calcium carbonate tartaric acid and
citric acid.
2.1. CLASSIFICATION OF FDDS
15. Figure 1. Mechanism of action in effervescent floating drug
delivery system.
2.1. CLASSIFICATION OF FDDS
e.g.Metronidazole tab using HPMC, Psyllium and
Carbopol for better eradication of Helicobacter
Pylori in peptic ulcer diseases.
17. Developed a floating afhizosin HCl multi-layer coated
tablets based on gas formation (Sungthongjeen et
al.,2008).
The system consists of a drug containing core tablet
coated with a protective layer (hydroxyl propyl methyl
cellulose), a gas forming layer (sodium bicarbonate)
and a gas entrapped membrane, respectively.
18. Goole(2008) developed and evaluated floating
minitablets (EMT) of levodopa prepared by melt
granulation and subsequent compression.
19. 2.swelling systems (non effervescent
systems)
Hydro dynamically balanced systems
(HBS) are the systems, containing one or
more gel forming hydrophilic polymers
which upon contact with the gastric fluids
swells and forms a colloidal gel barrier
resulting in low density.
2.1. CLASSIFICATION OF FDDS
21. The polymer is mixed with drug and usually
administered in a gelatin capsule. The capsule
rapidly dissolves in the gastric fluid, and
hydration and swelling of the surface polymers
produces a floating mass (Bardonnet et al.,
2006).
Continuous erosion of the surface allows
water penetration to the inner layers,
maintaining surface hydration and buoyancy
(Figure ).
2.swelling systems (non effervescent
systems)
22. Finally, an impermeable polypropylene cylinder was
developed having 10–15 mm length, sealed on both sides by a
matrix of hydrophilic polymer (HPMC) containing the drug.
Air entrapped in the core of the cylinder provided the
Buoyancy (Figure 17.b).
2.swelling systems (non effervescent
systems)
23. 3. inherent low density System
It is always desired that the drug delivery system
could float immediately upon contact with gastric
fluid which will reduced the risk associated with other
floating systems.
To achieve this, the low density should be provided
from the beginning either by:
the entrapment of air (hollow chamber) or by
the incorporation of low density material like oils
or foam powder (Bardonnet et al., 2006).
2.1. CLASSIFICATION OF FDDS
24. 3. inherent low density System
Fluid- filled floating chamber (Joseph et al., 2002) which includes
incorporation of a gas-filled floatation chamber into a microporous
component that houses a drug reservoir. The openings are present
along the top and bottom walls through which the gastrointestinal
tract fluid enters to dissolve the drug.
25. The highly porous foam powder provides a low
density of the system for at least 8 hrs in 0.1 N HCl at
37 C.
3. inherent low density System
26. Floating microparticles consisting of
polypropylene foam powder;
verapamil HCl as the model drug; and
Eudragit RS, EC or poly (methyl methacrylate)
(PMMA) were prepared with an
oil-in-water solvent extraction/ evaporation
method.
3. inherent low density System
27. Kawashima et al., 1992; Sato et al., 2003) developed
the hollow microspheres (microballoons) consisting of
eudragit S (an enteric polymer) containing the drug in
the polymeric shell.
As they possess the unique
advantages of multiple unit
systems as well as
better floating properties,
because of central hollow space
inside the microsphere.
Can float for 12-15 hours.
simple solvent evaporation, and solvent
diffusion and evaporation
3. inherent low density System
28. Cholrpheniramine
maleate,Theophylline, Furosemide,Ciprofloxacin, Ca
ptopril,Acetylsalicylic acid, Nimodipine,Amoxycillin
trihydrate, VerapamilHCI, Isosorbide di
nitrate, Sotalol,Isosorbide mononitrate,
Aceraminophen, Ampicillin,Cinnarazine, Dilitiazem,
Florouracil,
Piretanide, Prednisolone
Tablets
Nicardipine, L-Dopa and benserazide,chlordizepoxide
HCI, Furosemide,Misoprostal, Diazepam,
Propranlol,Urodeoxycholic acid.
Capsules
Aspirin, Griseofulvin, and pnitroanilline,Ketoprofen,
Tranilast,
Iboprufen, Terfenadine.
Microspheres
TABLE 1: List of Drugs Formulated as Single and Multiple Unit Forms of Floating
Drug Delivery Systems
29. Floating Solid lipid microparticle systems
SLNs/SLMs formulates into a
hydrodynamically balanced capsule, which is a
gastroretentive dosage form for prolonging the
release of administration.
Ofloxacin loaded SLNs were prepared using
palmitic acid as lipid matrix
and polyvinyl alcohol
(PVA) as emulsifier by
a hot homogenization and
ultrasonication method.
30. 1. Improved drug absorption, because of increased GRT
and more time spent by the dosage form at its absorption
site.
2. Controlled delivery of drugs.
3. Delivery of drugs for local action in
the stomach.
4. Minimizing the mucosal irritation due
to drugs, by drug releasing slowly at controlled rate.
5. Treatment of gastrointestinal disorders such as gastro-
esophageal reflux.
6. Simple and conventional equipment for manufacture.
7. Ease of administration and better patient compliance.
8. Site-specific drug delivery.
2.2. ADVANTAGES OF FDDS
31. 1. Gastric retention is influenced by many factors such as
gastric motility , pH and presence of food. These factors
are never constant and hence the buoyancy cannot be
predicted.
DISADVANTAGES OF FDDS
32. 2. Drugs that cause irritation and lesion to gastric mucosa are
not suitable to be formulated as FDDS.
3. Gastric emptying of floating forms in supine subjects may
occur at random and becomes highly dependent on the
diameter and size. Therefore patients should not be dosed with
floating forms just before going to bed.
DISADVANTAGES OF FDDS
33. 1- Dissertation on Development of extended release
multiple unit effervescent floating drug delivery
systems for drugs with different solubility. Samar
Elsamaligy 2010
2- Article of the Development And In Vitro Evaluation
Of Gastroretentive Floating Tablets Of
Famotidine.2011
Na bicarbonate 40,30mg citric acid and PVP K30 10mg
was found to be the best formulation in terms of drug
release and in vitro buoyancy time with stability
studies.
3. SOME ARTICLES AND RESEARCHES
34. 3- Article of Formulation and Evaluation Of Floating
Drug Delivery System Of Famotidine BK Satishbabu
India 2011
floating beads of famotidine ,cod liver oil entrapped Ca
alginate beads were promising as a carrier for
intragastric floating DD of famotidine.
4- Preparation of a Matrix type Multiple unit GRFDDS
for Captopril Based on Gas Formation Technique:In
Vitro Evaluation 2008 Lingam Meka
3. SOME ARTICLES AND RESEARCHES
35. 3. SOME ARTICLES AND RESEARCHES
5- Prolonged Gastro Delivery of Vitamin B2 from a
Floating DDS:An in Vitro Study , 2007, Sunil
6- Design and In-Vitro Evaluation of Cefuroxime Axetil
Floating Microbeads for the Treatment of Hospital
Acquired Infection, 2012, Mohapatra
7- Design and Evaluation of Bilayer Floating tablets of
Cefuroxime axetil for bimodal release,2006,Ravindra
8- Development and Evaluation of a Monolithic Floating
DDS for Acyclovir, 2011,Naser
