PRESENTED BY:

Mr. SOMNATH A. PATIL

M. Pharm 2nd semester

MAEER’S MAHARASHTRA INSTITUTE OF
PHARMACY, PUNE
 INTRODUCTION

 APPROACHES

 EVALUATION

 CONCLUSION

 REFERENCES
 The control of gastrointestinal transit of orally administered
dosage forms using gastroretentive drug delivery systems
(GRDDS) can improve the bioavailability of drugs that
exhibit site-specific absorption.

 Prolonged gastric retention can be achieved by using

floating, swelling, bioadhesive, or high-density systems.
 These are drug delivery system which possesses the
ability of retaining drug in GIT particularly in the
stomach for prolonged period of time .

 After the drug release for required period the dosage

form should get degraded without causing any gastric
disturbances.
NEED FOR GASTRORETENTIVE
DRUG DELIVERY SYSTEM

 A controlled drug delivery system with prolonged residence

time in the stomach is of particular interest for drugs
which……..

 Are locally active in the stomach (misoprostol, antacids,

antibiotics against H.pylori).
 Have an absorption window in stomach or in the upper
small intestine (L-dopa, P-aminobenzoic acid,
furosemide).Are unstable in the intestine or colonic
environment (captopril).
 Exhibit low solubility at high pH values (diazepam,
verapamil).
 Alter normal flora of the colon (antibiotics).
 Absorbed by transporter mechanism (paclitaxel).
ADVANTAGES:

 Improved drug absorption, because of increased GRT and more

time spent by the dosage form at its absorption site.

 Controlled delivery of drugs.

 Delivery of drugs for local action in the stomach.

 Minimizing mucosal irritation by drugs, by drug releasing

slowly at a controlled rate.

 Treatment of gastrointestinal disorders such as gastro-

esophageal reflux.

 Ease of administration and better patient compliance.

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.
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 interdigestive motility pattern that is
commonly called migrating motor complex (MMC).
 This is a series of events that cycle through the stomach
and small intestine every 1.2 to 2hrs.
 In the fed state, the gastric emptying rate is slowed down
because the onset of MMC is delayed, the feeding state results
in a lag time prior to onset of gastric emptying.
 Size of dosage form-better GRT is possessed by
1)Tetrahydron shaped devices
2)Single or multicomponent dosage form : The
multicomponent dosage form shows more effect comparing to
single dosage form.

 Density
 Food intake and nature of food-high meal is responsible
for GRT disturbance.
 Age –elder people have significant larger GRT.
 High density system

 Floating systems

 Expandable systems

 Superporous hydrogels

 Bioadhesive systems

 Magnetic systems
 Gastric contents have a density close to water (~1.004).
 A density close to 2.5g/cm3 is necessary for significant
prolongation of gastric residence time.
 The commonly used excipients in high density system
includes barium sulphate, zinc oxide, iron powder, and
titanium dioxide.
 The major drawback with such systems is that it is
technically difficult to manufacture them with a large
amount of drug (>50%) and to achieve the required density
of 2.4-2.8g/cm3.
Single-unit floating dosage system
 Non effervescent systems
 Effervescent (gas-generating) systems

Multiple-unit floating dosage system

 Hollow microspheres

Raft-forming systems
Single-Unit Floating Dosage System
Noneffervescent Systems :

 These systems contain one or more hydrocolloids and are

made into a single unit along with drug and other additives.

 When comes in contact with water, the hydrocolloids at the

surface of the system swell and facilitate floating.

 The coating forms a viscous barrier, and the inner polymer

slowly gets hydrated as well, facilitating the controlled drug
release. Such systems are called “hydrodynamically
balanced systems (HBS)”.

 The polymers used in this system includes

hydroxypropylmethylcellulose,hydroxyethylcellulose,
hydroxypropylcellulose, sodium carboxymethylcellulose,
agar, carrageenans, and alginic acid.
GAS GENERATING SYSTEM

 Carbonates or bicarbonates, which react with gastric acid or

any other acid (e.g., citric or tartaric) present in the
formulation to produce CO2, are usually incorporated in the
dosage form, thus reducing the density of the system and
making it float on the media.

 The main drawback of single unit dosage systems are high

variability of gastrointestinal transit time when orally
administered because of all-or-nothing nature of their
gastric emptying.
Multiple-Unit Floating Systems

Hollow Microspheres :

 Hollow microspheres possess the unique advantages of

multiple-unit systems and better floating properties as a
result of the central hollow space inside the microsphere.

 The general techniques involved in their preparation include

simple solvent evaporation and solvent diffusion and
evaporation.

 The drug release and better floating properties mainly

depend on the type of polymer, plasticizer, and solvent
employed for the preparation.

 Polymers such as polycarbonate, Eudragit S, and cellulose

acetate were used in the preparation of hollow microspheres.
 RAFT-FORMING SYSTEMS

 This system is used for delivery of antacids and drug delivery for
treatment of gastrointestinal infections and disorders.
 The mechanism involved in this system includes the formation of a
viscous cohesive gel in contact with gastric fluids, wherein each
portion of the liquid swells, forming a continuous layer called raft.
 This raft floats in gastric fluids because of the low bulk density
created by the formation of CO2.
 Usually the system contains a gel-forming agent and alkaline
bicarbonates or carbonates responsible for the formation of CO2 to
make the system less dense to float on the gastric fluids.
EXPANDABLE SYSTEM

These systems include Unfoldable and Swellable systems:

 Unfoldable systems are made of biodegradable polymers.

The concept is to make a carrier, such as a capsule,
incorporating a compressed system which extends in the
stomach.

 Caldwell et al. proposed different geometric forms

(tetrahedron, ring or planar membrane [4-lobed, disc or 4-
limbed cross form] ) of bioerodible polymer compressed
within a capsule.
 Swellable systems are retained because of their
mechanical properties. The swelling is usually results
from absorption of water.
 The dosage form is small enough to be swallowed, and
swells in gastric liquids. The bulk enables gastric
retention and maintain the stomach in fed state,
suppressing housekeeper waves.
 The whole system is coated by an elastic outer
polymeric membrane which was permeable to both
drug and body fluids and could control the drug release.
 The device gradually decreases in volume and rigidity
as a result depletion of drug and expanding agent or
bioreosion of polymer layer, enabling its elimination.
SUPERPOROUS HYDROGELS:
 Swellable agents with pore size ranging between 10nm and
10µm, absorption of water by conventional hydrogel is very
slow process and several hours may be needed to reach as
equilibrium state during which premature evacuation of the
dosage form may occur.
 Superporous hydrogels swell to equilibrium size with in a
minute, due to rapid water uptake by capillary wetting
through numerous interconnected open pores.
 They swell to large size and are intended to have sufficient
mechanical strength to withstand pressure by the gastric
contraction.
 This is achieved by co-formulation of a hydrophilic
particulate material.
 MUCOADHESIVE SYSTEM:

 The technique involves coating of microcapsules with

bioadhesive polymer, which enables them to adhere to
intestinal mucosa and remain for longer time period in the GI
while the active drug is released from the device matrix.

Polymer

Mucus membrane
MAGNETIC SYSTEM :

 This system is based on a simple idea: the dosage form

contains a small internal magnet, and a magnet placed on
the abdomen over the position of the stomach.

 Although these systems seem to work, the external magnet

must be positioned with a degree of precision that might
compromise patient compliance.
 Various parameters that need to be evaluated in
gastroretentive formulation include dissolution profiles,
specific gravity, content uniformity, hardness, and friability
in case of solid dosage forms.

 In case of multi particulate drug delivery systems,

differential scanning calorimetry, particle size analysis, flow
properties, surface morphology, and mechanical properties
are also performed.

 The tests for floating ability and drug release are generally
performed in simulated gastric fluids at 37 C.
Methods to asses gastroretentivity of
GRDFs:

Magnetic Resonance Imaging:

 It is a noninvasive technique and allow observation of total
anatomical structure in relatively high resolution.
 The visualization of GI tract by MRI has to be further
improved by the administration of contrast media.
 For solid DFs, the incorporation of a superparamagnetic
compound such as ferrous oxide enables their visualization
by MRI.

Radiology (X-Ray):
 In this technique a radio-opaque material has to be
incorporated in the DF, and its location is tracked by X-ray
picture.
ɣ-Scintigraphy:
 Gamma scintigraphy relies on the administration of a DF
containing a small amount of radioisotope,
e.g..,152Sm,which is a gamma ray emitter with a relatively
short half life.

Gastroscopy:
 Gastroscopy is commonly used for the diagnosis and
monitoring of the GI tract.
 This technique utilizes a fiberoptic or video system and can
be easily applied for monitoring and locating GRDFs in the
stomach.
Swelling studies:

 Tablets weighed individually (W1) and placed in Petri

dishes containing 15ml of 0.1N HCl. At regular intervals
they are removed from Petri dishes and excess surface
water was removed using filter paper
 The swollen tablets were reweighed (W2). The swollen
tablets are dried at 60 C at 24hrs in an oven and kept in
desiccators for 24hrs and reweighed (W3).
 Degree of swelling = W2 - W1
W1
 %Erosion = W1 - W3 X 100
W1
 The buoyancy time & duration of buoyancy is
performed in u.s.p dissolution apparatus 2 in simulated
fluid & 0.1N HCL maintained at 37˚C environment.

 Time interval between the introduction of tablet in

dissolution media. It s buoyancy to the dissolution media
was taken as buoyancy lag time.
Brand Name Active Ingredient(s)
Cifran OD ®
Madopar ®
Valrelease ®
Topalkan ®
Almagate FlatCoat ®
Liquid Gavison ®
ConvironCytotec®
Microcapsules
drug located centrally within
the particle, where it is
encased within a unique
polymeric membrane as a
drug located centrally within
the particle, where it is
encased within a unique
polymeric membrane
Microsphere
has its drug dispersed
throughout the particle i.e.
the internal structure is a
matrix of drug and
polymeric excipients
 Microspheres can be defined as solid, approximately
spherical particles ranging in size from 1 to 1000 µm.
They are made from polymeric, waxy, or other
protective materials such as starches, gums, proteins,
fats and waxes and used as drug carrier matrices for
drug delivery. Natural polymers as albumin and gelatin
are also used in preparation of microspheres.
 Controlled release delivery Biodegradable microspheres
are used to control drug release rates thereby decreasing
toxic side effects, and eliminating the inconvenience of
repeated injections.

 Biodegradable microspheres have the advantage over

large polymer implants in that they do not require
surgical procedures for implantation and removal.

 PLGA copolymer is one of the synthetic biodegradable

and biocompatible polymers that has reproducible and
slow-release characteristics in vivo .
1-Chitosan
2-Gelatine
3-Polyadipic anhydride
4-Gellan- gum
5-Polypeptide
6-Albumin
7-Poly lactic acid (PLA)
8-Poly lactic - co- glycolic acid (PLGA)
 Microspheres prepared by using Calcium chloride
solution
 Microspheres delivery system for theophylline using
emulsification solvent diffusion system .
 Chitosan microcapsule containing theophylline &sodium
carboxy methyl cellulose prepared by emulsion phase
separation method.
 Clarithromycin floating beads prepared by emulsion
gelation methods .
 Microspheres have been prepared by three basic
methods as well as other modified methods:

 Solvent extraction / evaporation method (single and

double emulsification)

 Co acervation or phase separation.

 Spray drying.

 Modified methods.
 Oil phase (polymer + solvent) is injected into the
aqueous phase (water + surfactant), the solvent dissolves
into the aqueous phase and evaporates at the air-liquid
interface.

 This method was successfully used for numerous of

water insoluble and slightly soluble drugs encapsulated
in microspheres such as lidocaine,lurbiprofen, all-trans
retinoic acid and testosterone.
The micro particulate carriers of natural polymers i.e.,
those of proteins and carbohydrates prepared by single
emulsion technique. The natural polymers are dissolved or
dispersed in aqueous medium followed by dispersion in
non-aqueous medium e.g.., oil.

In the second step of preparation cross-linking of the

dispersed globule is carried out. The cross linking can be
achieved either by means of heat or by using the chemical
crosslinkers.
Involves the formation of the multiple emulsions and is
best suited to the water-soluble drugs, peptides, proteins
and the vaccines. The aqueous protein solution is
dispersed in a lipophilic organic continuous phase. This
protein solution may contain the active constituents..
The primary emulsion is then subjected to the
homogenization or the sonication before addition to the
aqueous solution of the polyvinyl alcohol (PVA).

e.g. proteins/peptides are conventional molecule are

successfully incorporated in to the microspheres.
 This method is based on dispersion of drug as solid or
organic solution in organic polymeric solution, then
addition of the second solvent in which the polymer is
insoluble where phase separation occurs and polymer
loaded with drug precipitate as microspheres.

 BSA is an example prototype for this method.

 In this technique the drug and polymer are mixed in a
solvent system, then the solvent is evaporated by
spraying the solution leaving the polymeric particles
loaded with the drug.

 This method generates heat so it is not suitable for heat

sensitive drugs.

 e.g. Fluconazole and tetracycline hydrochloride.

 The development of GRDDs can be advantageous for the
administration of some important drugs and significantly
improves their therapeutic outcome.

 Gastroretentivity of a DF can be achieved by the

development of devices that can be significantly expand
their volume by unfolding or swelling, adhering to gastric
mucosa, or have the suitable density to sink or float over the
gastric fluids.
 Vyas SP Khar RK.gastroretentive system ,in; controlled drug
delivery Vallabh Prakashan ,Delhi India .2006 p.197-217
 Chawla G, Gupta P, Bansal AK. Gastroretentive drug
delivery systems. In: Jain NK. editor. Progress in
controlled and novel drug delivery systems. CBS
Publishers and Distributors. New Delhi. 2004. p. 76-97.
 Encyclopedia of Pharmaceutical Technology..
 Julan UD. Floating Drug Delivery System: An Approach to
Gastroretension. Latest Reviews. 2007;5(1).
 Shweta A, Javed A, Alka A, Roop K, and Sanjula B. Floating
drug delivery systems: a review. AAPS PharmSciTech. 2005;6
(3) Article 47.
 Bhaskara R.jasti ,design of controlled release drug
delivery system ,M graw hill chemical engineering page
number 173-223.

 AV Mayavanshi &SS gajjar ,floating drug delivery

system to increase gastric retention time of drug ;A
Review 2008