INTRODUCTION
The
gastric emptying of dosage forms is an extreme-ly variable process and ability
to prolong and control the emptying time is a valuable asset for dosage forms
that reside in the stomach for a longer period of time than conventional dosage
forms. There are many difficulties faced in designing controlled release
systems for better absorption and enhanced bioavailability. One of such
difficulties is the inability to confine the dosage form in the desired area of
the gastrointestinal tract. Drug absorption from the gastrointestinal tract is
a complex procedure and is subject to many variables. It is widely acknowledged
that the extent of ga-strointestinal tract drug absorption is related to
contact time with the small intestinal mucosa (Hirtz, 1985). Thus, small
intestinal transit time is an important parameter for drugs that are incompletely
absorbed. Basic human physiology with the details of gastric emptying, motility
patterns, and physio-logical and formulation variables affecting the cosmic
emptying are summarized. Gastroretentive systems can remain in the gastric
region for several hours and hence significantly prolong the gastric residence
time of drugs. Prolonged gastric retention improves bioavailability, reduces
drug waste, and improves solubility for drugs that are less soluble in a high
pH environment. It has applications also for local drug delivery to the stomach
and proximal small intestines. Gastro retention helps to provide better
availability of new products with new therapeutic possibilities and substantial
benefits for patients. Based on these approaches, classification of floating
drug delivery systems (FDDS) has been described in detail. In vivo/in vitro
evaluation of FDDS has been discussed by scientists to assess the efficiency
and application of such systems. Several recent examples have been reported
showing the efficiency of such systems for drugs with bioavaila-bility
problems.
Basic Gastrointestinal Tract Physiology
Basically
stomach is divided into 3 regions: fundus, body, and antrum (pylorus). The
proximal part made of fundus and body acts as a reservoir for undigested
material, the antrum is the main site for mixing motions and act as a pump for
gastric emptying by propelling actions (Desai, 1984). 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 inter-digestive series of
electrical events take place, which cycle both through stomach and intestine
every
2 to 3 hours (Vantrappen et al., 1979). This is called the
inter-digestive myloelectric cycle or migrating myloelectric cycle (MMC), which
is further divided into following 4 phases as described by Wilson and
Washington (Wilson and Washing-ton, 1989)
Phase
I (basal
phase) lasts from 40 to 60 minutes with rare contractions. Phase II (pre-burst
phase) lasts for 40 to 60 minutes with intermittent action potential and
contractions. As the phase progresses the intensity and frequency also
increases gradually. Phase III (burst phase) lasts for 4 to 6 minutes.
It includes intense and regular contractions for short period. It is due to
this wave that all the undigested material is swept out of the stomach down to
the small intestine. It is also known as the housekeeper wave. Phase IV lasts
for 0 to 5 minutes and occurs between phases III and I of 2 consecutive cycles.
After
the ingestion of a mixed meal, the pattern of contractions changes from fasted
to that of fed state. This is also known as digestive motility pattern and
comprises continuous contractions as in phase II of fasted state. These
contractions result in reducing the size of food particles (to less than 1 mm),
which are propelled toward the pylorus in a suspension form. During the fed
state onset of MMC is delayed resulting in slowdown of gastric emptying rate
(Desai and Bolton, 1993). Scintigraphic studies determining gastric emptying
rates revealed that orally administered controlled release dosage forms are
subjected to basically 2 complications, that of short gastric residence time
and unpredictable gastric emptying rate.
CLASSIFICATION
OF DRUG DELIVERY SYSTEM
A.
Single Unit Floating Dosage Systems
a)
Effervescent Systems (Gas-generating Systems)
b) Non-effervescent Systems
B.
Multiple Unit Floating Dosage Systems
a)
Non-effervescent Systems
b)
Effervescent Systems (Gas-generating Systems)
c)
Hollow Microspheres C. Raft Forming Systems.
A.
Single Unit Floating Dosage Systems
a) Effervescent Systems
(Gas-generating Systems) :- These buoyant systems utilized
matrices prepared with swellable polymers like HPMC, polysaccha-rides like
chitosan, effervescent components like sodium bicarbonate, citric acid and
tartaric acid or chambers containing a liquid that gasifies at body
temperature. The optimal stoichiometric ratio of citric acid and sodium
bicarbonate for gas genera-tion is reported to be 0.76:1. The common approach
for preparing these systems involves resin beads loaded with bicarbonate and
coated with ethylcellu-lose. The coating, which is insoluble but permeable,
allows permeation of water. Thus, carbon dioxide is released, causing the beads
to float in the stomach (Rubinstein and Friend, 1994). Excipients used most
commonly in these systems include HPMC, polya-crylate polymers, polyvinyl
acetate, Carbopol®, agar, sodium alginate, calcium chloride, polyethy-lene
oxide and polycarbonates.
b)
Non-Effervescent Systems
This
type of system, after swallowing, swells unrestrained via imbibition of gastric
fluid to an extent that it prevents their exit from the stomach. These systems
may be referred to as the ‘plug-type systems’ since they have a tendency to
remain lodged near the pyloric sphincter. One of the formulation methods of
such dosage forms involves the mixing of 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. Examples of this type of FDDS include colloidal gelbarrier
(Rubinstein and Friend, 1979), micropor-ous compartment system (Roy, 1977),
alginate beads (Whitehead et al., 1998), and hollow microspheres (Sato
and Kawashima, 2003). Another type is a Fluid- filled floating chamber (Joseph et
al., 2002) which includes incorporation of a gas-filled floata-tion chamber
into a microporous component that houses a drug reservoir. Apertures or
openings are present along the top and bottom walls through which the
gastrointestinal tract fluid enters to dissolve the drug. The other two walls
in contact with the fluid are sealed so that the undissolved drug remains
therein. The fluid present could be air, under partial vacuum or any other
suitable gas, liquid, or solid having an appropriate specific gravity and an
inert behaviour. The device is of
Figure
1: Gas filled floatation chamber
swallowable
size, remains afloat within the stomach for a prolonged time and after the
complete release the shell disintegrates, passes off to the intestine, and is
eliminated.
A
newer self-correcting floatable asymmetric configuration drug delivery system
(Yang and Fassihi, 1996) has a 3-layermatrix to control the drug release. This
3-layer principle has been improved by development of an asymmetric
configuration drug delivery system in order to modulate the release extent and
achieve zero-order release kinetics by initially maintaining a constant area at
the diffusing front with subsequent dissolution/erosion toward the completion
of the release process. The system was designed in such a manner that it
floated to prolong gastric residence time in vivo, resulting in longer total
transit time within the gastrointestinal tract environment with maximum
absorptive capacity and consequently greater bioavailability. This particular
characteristic would be applicable to drugs that have pH-dependent solubility,
a narrow window of absorption, and are absorbed by active transport from either
the proximal or distal portion of the small intestine.
B.
Multiple Unit Floating Systems
In
spite of extensive research and development in the area of HBS and other
floating tablets, these systems suffer from an important drawback of high
variability of gastrointestinal transit time, when orally administered, because
of their all-or-nothing gastric emptying nature. In order to overcome the above
problem, multiple unit floating systems were developed, which reduce the
inter-subject variabili-ty in absorption and lower the probability of
dose-dumping. Reports have been found on the devel-opment of both
non-effervescent and effervescent
multiple unit systems (Iannuccelli et al., 1998). Much research
has been focused and the scientists are still exploring the field of hollow
microspheres, capable of floating on the gastric fluid and having improved
gastric retention properties.
Non-effervescent
Systems No much report was found in the literature on
non-effervescent multiple unit systems, as compared to the effervescent
systems. However, few workers have reported the possibility of developing such
system containing indomethacin, using chitosan as the polymeric excipient. A
multiple unit HBS containing indomethacin as a model drug prepared by extrusion
process is reported (Tardi and Troy, 2002). A mixture of drug, chitosan and
acetic acid is extruded through a needle, and the extrudate is cut and dried.
Chitosan hydrates and floats in the acidic media, and the required drug release
could be obtained by modifying the drug-polymer ratio.
B
) Effervescent Systems (Gas-generating Systems)
There
are reports of sustained release floating granules containing tetracycline
hydrochloride (Ikura et al., 1988).The granules are a mixture of drug
granulates of two stages A and B, of which A contains 60 parts of HPMC, 40
parts of polyacrylic acid and 20 parts of drug and B contains 70 parts of
sodium bicarbonate and 30 parts of tartaric acid. 60 parts by weight of
granules of stage A and 30 parts by weight of granules of stage B are mixed
along with a lubricant and filled into capsule. In dissolu-tion media, the
capsule shell dissolves and liberates the granules, which showed a floating time
of more than 8 h and sustained drug release of 80% in about6.5 h. Floating
minicapsules of pepstatin having a diameter of 0.1-0.2 mm has been reported by
Umezawa (Umezawa and Hamao, 1978). These minicapsules contain a central core
and a coating. The central core consists of a granule composed of sodium
bicarbonate, lactose and a binder, which is coated with HPMC. Pepstatin is
coated on the top of the HPMC layer. The system floats because of the CO2
release in gastric fluid and the pepstatin resides in the stomach for prolonged
period. Alginates have received much attention in the development of multiple
unit systems. Alginates are non-toxic, biodegradable linear copolymers composed
of L-glucuronic and L-mannuronic acid residues. A multiple unit system was
prepared (Iannuccelli et al., 1998)
Figure
2: (a) Different layers-Semi permeable membrane, Effervescent Layer, Core pill
layer,
(b) Mechanism of floatation viaCO2 generation.
comprises
of calcium alginate core and calcium alginate/PVA membrane, both separated by
an air compartment. In presence of water, the PVA leaches out and increases the
membrane permeabili-ty, maintaining the integrity of the air compartment.
Increase in molecular weight and concentration of PVA, resulted in enhancement
of the floating properties of the system.
Freeze-drying
technique is also reported for the preparation of floating calcium alginate
beads (Stops et al., 2008). Sodium alginate solution is added drop wise
into the aqueous solution of calcium chloride, causing the instant gelation of
the droplet surface, due to the formation of calcium alginate. The obtained
beads are freeze-dried resulting in a porous structure, which aid in floating.
The authors studied the behaviour of radio labeled floating beads and compared
with non-floating beads in human volunteers using gamma scintigraphy. Prolonged
gastric residence time of more than 5.5 h was observed for floating beads. The
non-floating beads had a shorter residence time with a mean onset emptying time
of 1h.
A
new multiple type of floating dosage system had developed having a pill in the
core, composed of effervescent layers and swellable membrane layers coated on
sustained release pills (shown in figure 2). The inner layer of effervescent
agents containing sodium bicarbonate and tartaric acid was divided into 2
sublayers to avoid direct contact between the 2 agents. These sublayers were
surrounded by a swellable polymer membrane containing polyvinyl acetate and
purified shellac. When this system was immersed in the buffer at 37°C, it
settled down and the solution permeated into the effervescent layer through the
outer swellable membrane. CO2 was generated by the neutralization reaction
between the 2 effervescent agents, producing swollen pills (like balloons) with
a density less than 1.0 g/ml (Ichikawa et al., 1991).
c)
Hollow Microspheres
Hollow
microspheres are considered as one of the most promising buoyant systems, as
they possess the unique advantages of multiple unit systems as well as better
floating properties, because of 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 the
solvents employed for the preparation. Polymers such as polycarbonate,
Eudragit® Sand cellulose acetate were used in the preparation of hollow
microspheres, and the drug release can be modulated by optimizing the poly-mer
quantity and the polymer-plasticizer ratio. Sustained release floating
microspheres using polycarbonate were developed (Thanoo et al., 1993),
employing solvent evaporation technique. Aspirin, griseofulvin and
p-nitroaniline were used as model drugs. Dispersed phase containing
polycarbonate solution in dichloromethane, and micronized drug, was added to
the dispersion medium containing sodium chloride, polyvinyl alcohol and
methanol. The dispersion was stirred for 3-4h to assure the complete solvent
evaporation, and the microspheres obtained were filtered, washed with coldwater
and dried. The spherical and hollow nature of the microspheres was confirmed by
Scanning electron microscopic studies. The microspheres showed a drug payload
of more than 50%, and the amount of
(a) (b)
(c)
Figure 3: Different
mechanisms of floating systems.
drug
incorporated is found to influence the particle size distribution and drug
release. The larger proportion of bigger particles was seen at high drug
loading, which can be attributed to the increased viscosity of the dispersed
phase.
C.
Raft Forming Systems
Raft
forming systems have received much attention for the delivery of antacids and
drug delivery for gastrointestinal infections and disorders. The basic
mechanism involved in the raft formation includes the formation of viscous cohesive
gel in contact with gastric fluids, wherein each portion of the liquid swells
forming a continuous layer called a raft. The raft floats because of the
buoyancy created by the formation of CO2 and act as a barrier to prevent the
reflux of gastric Contents like HCl and enzymes into the esophagus. Usually,
the system contains a gel forming agent and alkaline bicarbonates or
carbo-nates responsible for the formation of to make the system less dense and
float on the gastric fluids (Paterson et al., 2008).
MECHANISM
OF FLOATING SYSTEMS
There
are various attempts have been made to retain the dosage form in the stomach as
a way of increas-ing the retention time. These attempts include introducing
floating dosage forms (gas-generating systems and swelling or expanding
systems, mucoadhesive systems, high-density systems, modified shape systems,
gastric-emptying delaying devices and co-administration of gastric-emptying
delaying drugs. Among these, the floating dosage forms have been most commonly
used. Floating drug delivery systems (FDDS) have a bulk density less than
gastric fluids and so 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 (given in the Figure 3 (a)), 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 GRT
and a better control of the fluctuations in plasma drug concentration. Howev-er,
besides a minimal gastric content needed to allow the proper achievement of the
buoyancy retention principle, a minimal level of floating force (F) is also
required to keep the dosage form reliably buoyant on the surface of the meal.
To measure the floating force kinetics, a novel apparatus for determination of
resultant weight has been reported in the literature. The apparatus operates by
measur-ing continuously the force equivalent to F (as a function of time) that
is required to maintain the submerged object. The object floats better if F is
on the higher positive side (Figure 3(b)). This apparatus helps in optimizing
FDDS with respect to stability and durability of floating forces produced in
order to prevent the drawbacks of unforeseeable intragas-tric buoyancy
capability variations (Garg and Sharma, 2003).
F = F buoyancy - F gravity = (Df - Ds) gv
Where,
F= total vertical force
Df = fluid density
Ds
= object density
v
= volume and
g
= acceleration due to gravity
ADVANTAGES
OF FDDS SYSTEM
1.
The gastroretentive systems are advantageous for drugs absorbed through the
stomach, e.g. ferrous salts, antacids.
2.
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.
3.
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 empty-ing 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 intes-tine.
4.
The gastro retentive systems are advantageous for drugs meant for local action
in the stomach. e.g. antacids.
5.
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 advanta-geous to keep the drug in floating condition in
stomach to get a relatively better response.
6.
FDDS improves patient compliance by decreas-ing dosing frequency.
7.
Bioavailability enhances despite first pass effect because fluctuations in
plasma drug concentra-tion are avoided; a desirable plasma drug concentration
is maintained by continuous drug release.
8.
Better therapeutic effect of short half-life drugs can be achieved.
9.
Gastric retention time is increased because of buoyancy.
10.
Enhanced absorption of drugs which solubilize only in stomach.
11.
Superior to single unit floating dosage forms as such microspheres releases
drug uniformly and there is no risk of dose dumping.
12.
Avoidance of gastric irritation, because of sustained release effect,
floatability and uniform release of drug through multi particulate sys-tem.
EVALUATION
PARAMETERS OF STOMACH SPECIFIC FDDS
dosage
forms exhibit-ing gastric residence in vitro floating behaviour show prolonged
gastric residence in vivo. However, it has to be pointed There are different
studies reported in the literature indicate that pharmaceutical out that good
in vitro floating behaviour alone is not sufficient proof for efficient gastric
retention in vivo. The effects of the simulta-neous presence of food and of the
complex motility of the stomach are difficult to estimate. Obviously, only in
vivo studies can provide definite proof that prolonged gastric residence is
obtained.
1.
Measurement of buoyancy
capabilities of the FDDS The floating behaviour was
evaluated with resultant weight measurements. The experiment was carried out in
two different media, deionised water in order to monitor possible difference.
The apparatus and its mechanism are explained earlier in this article. The
results showed that higher molecular weight polymers with slower rate of
hydration had en-hanced floating behaviour and it was observed more in
simulated meal medium compared to de-ionized water.
2.
Floating time and dissolution The
test for floating time measurement is usually performed in stimulated gastric
fluid or 0.1 mole/ lit HCl maintained at 37°C. It is determined by using USP
dissolution apparatus containing 900 ml of 0.1mole/lit HCl as the dissolution
medium at 37°C. The time taken by the dosage form to float is termed as
floating lag time and the time for which the dosage form floats is termed as
the floating or flotation time (Karande and Yeole, 2006) A more relevant in-vitro
dissolution method pro-posed to evaluate a floating drug delivery system
(for tablet dosage form) (Gohel et al., 2004). A 100 ml glass beaker was
modified by adding a side arm at the bottom of the beaker so that the beaker
can hold 70 ml of 0.1 mol/lit HCl dissolution medium and allow collection of
samples. A burette was mounted above the beaker to deliver the dissolution
medium at a flow rate of 2 ml/min to mimic gastric acid secretion rate. The
performance of the modified dissolution apparatus was compared with USP
dissolution. Apparatus 2 (Paddle): The problem of adherence of the tablet to
the shaft of the paddle was observed with the USP dissolution apparatus. The
tablet did not stick to the agitating device in the proposed dissolution
method. The drug release followed zero-order kinetics in the proposed method.
Similarity of dissolution curves was observed between the USP method and the
pro-posed method at 10% difference level (f2=57). The proposed test may show
good in vitro-in vivo correlation since an attempt is made to mimic the in
vivo conditions such as gastric volume, gastric emptying, and gastric acid
secretion rate.
3.
Drug release Dissolution
tests are performed using the dissolu-tion apparatus. Samples are withdrawn
periodically from the dissolution medium with replacement and then analyzed for
their drug content after an appropriate dilution.
4. Content
uniformity, hardness, friability (for tablets)
5.Drug
loading, drug entrapment efficiency, particle size analysis, surface
characterization (for floating microspheres and beads) Drug
loading is assessed by crushing accurately weighed sample of beads or
microspheres in a mortar and added to the appropriate dissolution medium which
is then centrifuged, filtered and analyzed by various analytical methods like
spectrophotometry. The percentage drug loading is calculated by dividing the
amount of drug in the sample by the weight and simulated meal, total beads or
microspheres. The particle size and the size distribution of beads or
microspheres are deter-mined in the dry state using the optical microscopy
method. The external and cross-sectional morpholo-gy (surface characterization)
is done by scanning electron microscope (SEM) (Agnihotri et al., 2006).
6.
X-Ray/Gamma scintigraphy X-Ray/Gamma scintigraphy is a very
popular evaluation parameter for floating dosage form now a day (Fell and
Digenis, 1984). It helps to locate dosage form in the GIT and by which one can
predict and correlate the gastric emptying time and the passage of dosage form
in the GIT. Here the inclusion of a radio-opaque material into a solid dosage
form enables it to be visualized by X-rays. Similarly, the inclusion of a
γ-emitting radionuclide in a formulation allows indirect external observation
using a γ-camera or scinti-scanner (Harries and Sharma, 1990). In case of γ-scintigraphy,
the γ-rays emitted by the radionuclide are focused on a camera, which helps to
monitor the location of the dosage form in the GI tract (Timmermans et al.,
1989).
7. Pharmacokinetic studies
Pharmacokinetic studies are the integral part of the in vivo
studies and several works has been on that. The pharmacokinetics studies of
verapamil, from the loading pellets containing drug,
filled into a capsule, and compared with the conventional verapamil tablets of
similar dose (40 mg). The tmax and AUC (0-infinity) values (3.75h and 364.65
ng/mlh, respectively) for floating pellets were comparatively higher than those
obtained for the conventional verapamil tablets (tmax value 1.21h, and AUC
value 224.22ng/mlh) (Sawicki, 2002). No much difference was found between the
Cmax values of both the formulations, suggesting the improved bioavailability
of the floating pellets compared to the conventional tablets. An improve-ment
in bioavailability has also been observed with piroxicam in hollow
polycarbonate microspheres administered in rabbits. The microspheres showed
about 1.4 times more bioavailability, and the elimination half-life was
increased by about three times than the free drug.
FACTORS
CONTROLLING GASTRIC RETEN-TION OF DOSAGE FORMS
The
gastric retention time (GRT) of dosage forms is controlled by several factors
such as density and size of the dosage form, food intake, nature of the food,
posture, age, sex, sleep and disease state of the individual (e.g.,
gastrointestinal diseases and diabetes) and administration of drugs such as
prokinetic agents (cisapride and metoclopramide).
1.
Density of dosage form Dosage
forms having a density lower than that of gastric fluid experience floating
behavior and hence gastric retention. A density of <1.0 gm/cm3 is required
to exhibit floating property. However, the floating tendency of the dosage form
usually decreases as a function of time, as the dosage form gets immersed into
the fluid, as a result of the development of hydrodynamic equilibrium
(Tim-mermans and Moes, 1990).
2. Size of
dosage form
The size of
the dosage form is another factor that influences gastric retention. The mean
gastric residence times of non-floating dosage forms are highly variable and
greatly dependent on their size, which may be small, medium, and large units.
In fed conditions, the smaller units get emptied from the stomach during the
digestive phase and the larger units during the housekeeping waves. In most
cases, the larger the size of the dosage form, the greater
will be the gastric retention time because the larger size would not allow the
dosage form to quickly pass through the pyloric antrum into the intestine
(El-Kamel et al., 2001). Thus the size of the dosage form appears to be
an important factor affecting gastric retention.
2.
Food intake and nature of food Food
intakes, the nature of the food, caloric content, and frequency of feeding have
a profound effect on the gastric retention of dosage forms. The presence or
absence of food in the stomach influences the GRT of the dosage form. Usually,
the presence of food increases the GRT of the dosage form and increases drug
absorption by allowing it to stay at the absorption site for a longer time. In
a gamma scintigraphic study of a bilayer floating capsule of misoprostol (Oth et
al., 1992), the mean gastric residence time was 199 ± 69 minutes; after a
light breakfast, a remarkable enhancement of average GRT to 618 ± 208 minutes
was observed.
3.
Effect of gender, posture and age A
study (Mojaverian et al., 1988) found that females showed comparatively
shorter mean ambulatory GRT than males, and the gastric emptying in women was
slower than in men. The authors also studied the effect of posture on GRT, and
found no significant difference in the mean GRT for individu-als in upright,
ambulatory and supine state. On the other hand, in a comparative study in
humans, the floating and non-floating systems behaved different-ly (Gansbeke et
al., 1991). In the upright position, the floating systems floated to the
top of the gastric contents and remained for a longer time, showing prolonged
GRT. But the non-floating units settled to the lower part of the stomach and
underwent faster emptying as a result of peristaltic contractions, and the
floating units remained away from the pylorus. However, in supine position, the
floating units are emptied faster than non-floating units of similar size
(Timmermans and Moes, 1994).
APPLICATION OF FDDS
Floating drug delivery
offers several applications for drugs having poor bioavailability because of
the narrow absorption window in the upper part of the gastrointestinal tract.
It retains the dosage form at the site of absorption and thus enhances the
bioavai-lability. These are summarized as follows:
1. Sustained Drug
Delivery HBS systems can remain in the stomach for long
periods and hence can release the drug over a prolonged period of time. The
problem of short gastric residence time encountered with an oral CR formulation
hence can be overcome with these systems. These systems have a bulk density of
<1 as a result of which they can float on the gastric contents. These
systems are relatively large in size and passing from the pyloric opening is
prohibited.
2. Site-Specific Drug
Delivery These systems are particularly advantageous for
drugs that are specifically absorbed from stomach or the proximal part of the
small intestine, e.g., riboflavin and furosemide. Furosemide is primarily
absorbed from the stomach followed by the duode-num. It has been reported that
a monolithic floating dosage form with prolonged gastric residence time was
developed and the bioavailability was in-creased. AUC obtained with the
floating tablets was approximately 1.8 times those of conventional furosemide
tablets.
3. Absorption
Enhancement Drugs that have poor bioavailability
because of site specific absorption from the upper part of the gastrointestinal
tract are potential candidates to be formulated as floating drug delivery
systems, thereby maximizing their absorption. E.g. A significantly increase in
the bioavailability of floating dosage forms (42.9%) could be achieved as
compared with commercially available LASIX tablets (33.4%) and enteric coated
LASIX-long product (29.5%) (Moursy et al., 2003).
CONCLUSION
The FDDS become an
additional advantage for drugs that are absorbed primarily in the upper part of
GI tract, i.e., the stomach, duodenum, and jejunum. Drug absorption in the
gastrointestinal tract is a highly variable procedure and prolonging gastric
retention of the dosage form extends the time for drug absorption. FDDS
promises to be a poten-tial approach for gastric retention. It seems that to
formulate an efficient FDDS is sort of a challenge and the work will go on and
on until an ideal approach with industrial applicability and feasibili-ty
arrives.
REFRENCES
Timmermans,
J., Moes, A.J. (1990). How well do floating dosage forms float?, Int J Pharm.
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Iannuccelli,
V., Coppi, G., Sansone, R., Ferolla, G. (1998). Air compartment multiple-unit
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Pharm. 174:55-62. DOI
Iannuccelli, V., Coppi, G., Bernabei, M.T., Cameroni, R. (1998)
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