23-06-2014, 02:56 PM
THE PHARMA INNOVATION Review on Gastro Retentive Drug Delivery System
THE PHARMA INNOVATION.pdf (Size: 511.67 KB / Downloads: 74)
INTRODUCTION
Oral route of drug
administration is the most convenient and
commonly used method of drug delivery.
However, this route has several physiological
problems.
Corresponding Author’s Contact information:
A. Badoni *
Division of Pharmaceutical sciences, Shri Guru Ram Rai
Institute of Technology & Science, Patel Nagar, Dehradun
(Uttrakhand)
E-mail: ashishbadoni44[at]gmail.com
Including an unpredictable gastric emptying rate
that varies from person to person, a brief
gastrointestinal transit time (80-12h), and the
existence of an absorption window in the upper
small intestine for several drugs.1
These difficulties have prompted researchers to
design a drug delivery system which can stay in
the stomach for prolonged and predictable period.
Attempts are being made to develop a drug
delivery system which can provide
therapeutically effective plasma drug
concentration for a longer period, thereby
ANATOMY OF THE GASTROINTESTINAL TRACT
The gastrointestinal tract can be divided into
three main regions namely
1. Stomach
2. Small intestine- Duodenum, Jejunum and
Ileum
3. Large intestine
The GIT is a continuous muscular tube, extending
from the mouth to the anus, which functions to
take in nutrients and eliminate waste by such
physiological processes as secretion, motility,
digestion, absorption and excretion. The
organization of the GIT, from stomach to large
intestine, is shown in Fig.1. The stomach is a Jshaped
enlargement of the GIT which can be
divided into four anatomical regions: cardia,
fundus, body and antrum. The main function of
the stomach is to store and mix food with gastric
secretions before emptying its load (chyme)
through the pyloric sphincter and into the small
intestine at a controlled rate suitable for digestion
and absorption. When empty, the stomach
occupies a volume of about 50 ml, but this may
increase to as much as 1 litre when full
MUCUS: STRUCTURE, FUNCTION AND COMPOSITION
Mucus is a complex viscous adherent secretion
which is synthesized by specialized goblet cells.
These goblet cells are glandular columnar
epithelium cells and line all organs that are
exposed to the external environment. Mucus is
found to serve many functions within these
locations such as lubrication for the passage of
objects, maintenance of a hydrated epithelium
layer, a barrier function with regard to pathogens
and noxious substances and as a permeable gel
layer allowing for the exchange of gases and
nutrients to and from underlying epithelium10.
BASIC GASTROINTESTINAL TRACT PHYSIOLOGY14
regions:
Fundus,
Body, and
Antrum pylorus.
The proximal part made of fundus and body acts
as a reservoir for undigested material, whereas
the antrum is the main site for mixing motions
and acts as a pump for gastric emptying by
propelling actions. Gastric emptying occurs
during fasting as well as fed states. The pattern of
motility is however distinct in the 2 states.
During the fasting state an interdigestive series of
electrical events take place, which cycle through
both stomach and intestine every 2 to 3 hours.
This is called the interdigestive myloelectric
cycle or migrating myloelectric cycle (MMC),
which is further divided into following 4 phases
CERTAIN TYPES OF DRUGS CAN BENEFIT FROM USING GASTRIC RETENTION DEVICES. These include drugs that
Are acting locally in the stomach e.g.
Antacids and drugs for H.pylori viz.
Misoprostol
Primarily absorbed in the stomach. e.g.
Amoxicillin
Have an absorption window in the
stomach or in the upper small intestine,
Drugs with narrow window of
absorption, e.g. Cyclosporine, Methotrexate,
Levodopa
Are unstable in the intestinal or colonic
environment, e.g. Ranitidine, Metformin Hcl
Exhibit low solubility at high pH values.
SWELLING SYSTEM
These are the dosage forms, which after
swallowing, swells to an extent that prevents their
exit from the pylorus. As a result, the dosage
form is retained in the stomach for a longer
period of time. These systems may be named as
‘plug type systems’, since they exhibit the
tendency to remain logged at the pyloric
sphincter if that exceed a diameter of
approximately 12-18mm in their expanded state.
The balance between the extent and duration of
swelling is maintained by the degree of cross
linking between the polymeric chains. A high
degree of cross – linking retards the swelling
ability of the system maintaining its physical
integrity for prolonged period.
SUPER POROUS HYDROGEL SYSTEM
These swellable systems differ significantly from
the conventional types to hold a separate
classification. In this approach to improve the
GRT super porous hydrogels of average pore size
> 100 micrometer, swell to equilibrium size
within a minute due to the rapid water uptake by
capillary wetting through numerous
interconnected open pores. They swell to large
size (swelling ratio: 100 or more) and are
intended to have sufficient mechanical strength to
withstand pressure by gastric contraction. This is
advised by co-formulation of hydrophilic
particulate material
CONCLUSION
Based on the literature survey, it can be
concluded that GRDDs offers various potential
advantages for drugs with poor bioavailability.
Drug absorption in the gastro intestinal tract is a
highly variable process and prolonging gastric
retention of the dosage form extends the time for
drug absorption.
The control of gastro intestinal transit of orally
administered dosage forms using GRDD systems
can improve the bioavailability of drugs that
exhibit site specific absorption. GRDFs also
provide an additional advantage for drugs that are
absorbed primarily in the upper segment of GIT,
i.e., stomach, duodenum and jejunum.
Different approaches for GRDD are studied each
having their own advantages and disadvantages.
Due to unpredictability of human GIT
development of efficient GRDFs is a real
challenge to pharmaceutical technology as the
drug delivery system must remain for a sufficient
time in the stomach which is not compatible with
normal physiology.
In the future it is can be easily assumed that
GRDD systems will become more popular in
terms of delivering drug to the systemic
circulation with improving efficiency of various
type of pharmacotherapy’s.