FDDS
Intruduction
GRT & GER
• Gateric residence time
• Gasteric empty rate
APPROACHES TO GASTRIC RETENTION:
1. Floating drug delivery systems (FDDS): These
systems have low density and so float over the
gastric contents.
2. Bioadhesive systems: They bind with stomach
mucosa and hence, enable the localized retention
of the system.
3. Swelling and expanding systems: Such systems
absorb water and hence, enlarged size.
4. High density systems: They remain in the stomach
for longer period of time, by sedimenting to the
folds of stomach.
importance
• Predetermined predictable and controlled
release
• maintenance of optimum therapeutic drug
concentration in blood
• enhancement of activity and duration for short
Half-Life drugs
• reducing frequency of dosing and wastage of
drugs
• optimise therapy and better patient compliance
Definition
• Floating drug delivery systems (FDDS) or hydro
dynamically controlled systems are low-density systems
that have sufficient buoyancy to float over the gastric
contents and remain buoyant in the stomach without
affecting the gastric emptying rate for a prolonged period
of time. While the system is floating on the gastric
contents, the drug is released slowly at the desired rate
from the system. After release of drug, the residual
system is emptied from the stomach. This results in an
increased Gastric retention time
Mechanism of floating systems
FDDS can be divided into non-effervescent
and gas-generating system:
(a)Non-effervescent systems
(b)Effervescent systems
A.Non-effervescent systems:
(i) Colloidal gel barrier system
(ii) Microporous compartment system
(iii) Alginate beads
(iv) Hollow microspheres / Microballons
Non-effervescent systems
This type of system, after swallowing, swells
unrestrained via imbibitions of gastric fluid to an
extent that it prevents their exit from the stomach.
One of the formulation methods of such dosage
forms involves the mixing of the drug with a gel,
which swells in contact with gastric fluid after oral
administration and maintains a relative integrity of
shape and a bulk density of less than one within the
outer gelatinous barrier. The air trapped by the
swollen polymer confers buoyancy to these dosage
forms.
Colloidal gel barrier system
Such a system contains drug with gel-forming hydrocolloids
meant to remain buoyant on the stomach content. This
prolongs GRT and maximizes the amount of drug that
reaches its absorption sites in the solution form for ready
absorption. This system incorporates a high level of one or
more gel-forming highly soluble cellulose type hydrocolloid,
e.g., hydroxypropyl cellulose, hydroxyethyl cellulose,
hydroxypropyl methyl cellulose (HPMC), polysaccharides
and matrixforming polymer such as polycarbophil,
polyacrylate and polystyrene. On coming in contact with
gastric fluid, the hydrocolloid in the system hydrates and
forms a colloid gel barrier around its surface.
Microporous compartment system
This technology is based on 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. In the stomach, the floatation chamber
containing entrapped air causes the delivery system to float
over the gastric content. Gastric fluid enters through the
aperture, dissolves the drug and carries the dissolved drug
for continuous transport across the intestine for absorption.
Alginate beads
Multi-unit floating dosage forms have been developed from
freeze-dried calcium alginate. Spherical beads of
approximately 2.5 mm in diameter can be prepared by
dropping sodium alginate solution into aqueous solution of
calcium chloride, causing the precipitation of calcium
alginate. The beads are then separated, snap-frozen in
liquid nitrogen, and freeze-dried at -40ºC for 24 hours,
leading to the formation of a porous system, which can
maintain a floating force for over 12 hours. These floating
beads gave a prolonged residence time of more than 5.5
hours.
Hollow microspheres / Microballons
Hollow microspheres loaded with drug in
their outer polymer shelf were prepared by a
novel emulsion solvent diffusion method.
B.Effervescent systems:
(i) Volatile liquid containing systems
(ii)Gas-generating Systems
Volatile liquid containing systems
The GRT of a drug delivery system can be sustained by
incorporating an inflatable chamber, which contains a liquid
(like ether, cyclopentane), that gasifies at body temperature
to cause the inflatation of the chamber in the stomach. The
device may also consist of a bio-erodible plug made up of
PVA, Polyethylene, etc. that gradually dissolves and
causing
the inflatable chamber to release gas and collapse after a
predetermined time to permit the spontaneous ejection of
the
inflatable systems from the stomach.
Gas-generating systems
These buoyant systems utilize matrices
prepared with swellable polymers such as
methocel, polysaccharides (e.g., chitosan),
effervescent components (e.g., sodium
bicarbonate, citric acid or tartaric acid). The
system is so prepared that upon arrival in
the stomach, carbon dioxide is released,
causing the formulation to float in the
stomach.
Most of the floating systems are single unit
system; these systems are unreliable and
irreproducible in prolonging residence time
in the stomach when orally administered,
owing to their fortuitous (‘all-ornothing’)
emptying process. On the other hand,
multiple unit dosage forms appear to be
better option since they reduce the inter
subject variability in absorption and lower
the probability of dose dumping.
Factors controlling gastric retention of dosage forms
a) Density of dosage form
b) Size of dosage form
c) Food intake and nature of food
d) Effect of gender, posture and age
Applications of Floating Drug Delivery Systems
a) Sustained Drug Delivery
b) Site-Specific Drug Delivery
c) Absorption Enhancement
d) Enhanced bioavailability
e) Enhanced first-pass biotransformation
f) Sustained drug delivery/reduced frequency of
dosing
Applications of Floating Drug Delivery Systems
g) Targeted therapy for local ailments in the upper
GIT
h) Reduced fluctuations of drug concentration
i)Improved selectivity in receptor activation
j) Reduced counter-activity of the body
k) Extended time over critical (effective)
concentration
l) Minimized adverse activity at the colon
Advantages of Floating drug delivery
system
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The floating drug delivery systems are advantageous for drugs absorbed
through the stomach. E.g. Ferrous salts, antacids.
Acidic substances like aspirin cause irritation on the stomach wall when come
in contact with it. Hence HBS formulation may be useful for the administration
of aspirin and other similar drugs.
Administration of prolongs release floating dosage forms, tablet or capsules,
will result in dissolution of the drug in the gastric fluid. They dissolve in the
gastric fluid would be available for absorption in the small intestine after
emptying of the stomach contents. It is therefore expected that a drug will be
fully absorbed from floating dosage forms if it remains in the solution form
even at the alkaline pH of the intestine.
The floating drug delivery systems are advantageous for drugs meant for local
action in the stomach. E.g. antacids.
When there is a vigorous intestinal movement and a short transit time as
might occur in certain type of diarrhea, 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.
Disadvantages of floating
drug delivery systems
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Floating system is not feasible for those drugs that have solubility or stability
problem in GIT.
These systems require a high level of fluid in the stomach for drug delivery
to float and work efficiently.
Drugs such as Nifedipine which is well absorbed along the entire GIT and
which undergoes first pass metabolism may not be desirable.
Drugs which are irritant to gastric mucosa are not suitable.
Drug substances that are unstable in the acidic environment of the stomach
are not suitable candidates to be incorporated in the system.
The dosage form should be administered with a full glass of water (200-250
ml).
These systems do not offer significant advantages over the conventional
dosage forms for drugs which get absorbed throughout gastrointestinal
tract.
Suitable drug candidates for
gastroretention
In general, appropriate candidates for GRDDS are molecules
that have poor colonic absorption but are characterized by better
absorption properties at the upper parts of the GIT:
1. Narrow absorption window in GI tract e.g., riboflavin and
levodopa.
2. Primarily absorbed from stomach and upper part of GI tract,
e.g.,calcium supplements.
3. Drugs that act locally in the stomach, e.g., chlordiazepoxide
and cinnarazine.
4. Drugs that degrade in the colon, e.g., antacids and
misoprostol.
5. Drugs that disturb normal colonic bacteria ranitidine HCl and
metronidazole.
Marketed products of FDDS
Brand Name
Delivery System
Drug Dose
Val release®
Floating Capsule
Diazepam (15 mg)
Topalkan®
Floating liquid alginate
preparation
Al-Mg Antacid
Conviron®
Colloidal gel forming
FDDS
Ferrous sulphate
Cytotech®
Bilayer floating capsule
Misoprostol (100μg/200μg)
Cifran OD®
Gas generating floating
form
Ciprofloxacin(1gm)
Liquid Gaviscon®
Effervescent floating
liquid alginate
preparation
Al hydroxide (95mg), Mg
Carbonate (358mg)
Madopar HBS
Floating CR capsule
Levodopa & Benserazide
Conclusion
Drug absorption in the gastrointestinal tract is a highly variable
procedure and prolonging gastric retention of the dosage form
extend the time for drug absorption. They can be delivered
efficiently thereby capitalizing on their absorption and enhancing
absolute bioavailability. FDDS promises to be a potential
approach for gastric retention. FDDS is advantageous for drugs
that are absorbed primarily in the upper segment of GI tract i.e.
stomach, duodenum and jejunum when compared to the
conventional dosage forms. The increasing sophistication of
delivery technology will ensure the development of increase
number of gastroretentive drug delivery to optimize the delivery
of molecules that exhibit absorption window, low bioavailability
and extensive first pass metabolism.
Refrences
Katakam, J.M Somagoni, S. Reddy, C. M Eaga,B.R Chary
Rallabandi, M.R Yamsani(2010) Floating Drug Delivery
Systems: A Review
S. Gopalakrishnan and A. Chenthilnathan (2011) Floating Drug
Delivery Systems: A Review
Shweta Arora,1 Javed Ali,1 Alka Ahuja,1 Roop K. Khar,1 and
Sanjula Baboot(2005) Floating Drug Delivery Systems: A
Review
 Lenaerts VM, Gurny R. Gastrointestinal Tract- Physiological
variables affecting the performance of oral sustained release
dosage
forms. In: Lenaerts V, Gurny R, eds. Bioadhesive Drug Delivery
System.
Boca Raton, FL: CRC Press; 1990.
Refrences
Chawla, G., Gupta P., Koradia, V. andBansal, A. K. (2003).
Gastro retention: Ameans to address regional variabilitinin
intestinal drug absorption. Pharm.Tech., 50– 68.
Rouge, N., Buri, P. and Doelkar, E. (1996).Drug absorption site
in gastrointestinal trac tand dosage forms for site specific
delivery.Int.J.Pharm, 136(1): 117 – 139.
Hirtz, J. (1985).The GIT absorption of drug sin man: a review of
current concepts an dmethods of investigation. Br J
ClinPharmacol.; 19: 77S-83S.