Research J. Pharm. and Tech.

6(12): December 2013

ISSN 0974-3618 www.rjptonline.org

REVIEW ARTICLE

Floating Microspheres as Gastro-Retentive Drug Delivery System:

A Review
Sagar Firke*, Ashish Roge, Nitin Ghiware, S.B. Dhoot, S.M. Vadwalkar
CRPS, Nanded Pharmacy College, Nanded, Maharashtra
*Corresponding Author E-mail: sagar1385@yahoo.co.in

ABSTRACT:
Gatsroretentive drug delivery system offers several advantages besides providing better bioavailability to poorly
absorbed drugs and a required release profile thus attracting interest of pharmaceutical formulation scientists. A
controlled drug delivery system with prolonged residence time in the stomach can be of great practical importance for
drugs with an absorption window in the upper small intestine. Various gastroretentive dosage forms are available,
including tablets, capsules, pills, laminated films, granules and powders. Floating microspheres is one among the
several approaches to gastroretention, like mucoadhesion, flotation, sedimentation, expansion, modified shape systems
etc. Floating microspheres have been gaining attention due to the uniform distribution of these multiple-unit dosage
forms in the stomach, which results in more reproducible drug absorption and reduced risk of local irritation. Such
systems have more advantages over the single-unit dosage forms. The present review briefly addresses the physiology
of the gastric emptying process with respect to floating drug delivery systems. The purpose of this review is to bring
together the recent literature with respect to the method of preparation, and various parameters affecting the
performance and characterization of floating microspheres.

KEYWORDS: Floating microspheres. Emulsion solvent diffusion-evaporation method. Drug delivery system.
elease modifiers.

INTRODUCTION: Gastric emptying of dosage forms is an extremely variable

Among the different routes of drug administration, the oral
route has achieved the most attention, partly due to the ease
of administration and to the important flexibility in dosage
form design. The goal of any drug delivery system is to
provide a therapeutic amount of drug at the proper site in
the body and then maintain the desired drug concentration.
Unfortunately, in most cases, the important variability of
the gastrointestinal tract physiology and of its transit time
leads to unpredictable bioavailability and non reproducible
therapeutic effects1.
Most drugs are well absorbed throughout the entire
intestinal tract, but some compounds, usually those that are
polar in nature, are poorly absorbed from the large intestine.
For such drugs, the main area from which absorption occurs
is the small intestine. A major constraint in oral
controlled drug delivery is that, not all drug candidates
are absorbed uniformly throughout the Gastrointestinal
Tract.
Received on 29.09.2013 Modified on 15.10.2013
Accepted on 19.10.2013 © RJPT All right reserved
Research J. Pharm. and Tech. 6(12): Dec. 2013; Page 1452-1458
1452
process and the ability to prolong and control emptying
time is a valuable asset for dosage forms that reside in the
stomach for a longer period of time than conventional
dosage forms. Thus, control of placement of a short period
of DDS in a specific region of the GI tract offers numerous
advantages, especially for drugs exhibiting an absorption
window in the GI tract or drugs with a stability problem.
Gastroretentive systems can remain in the gastric region for
several hours and hence significantly prolong the gastric
residence time of drugs. Prolongation of gastric residence
time (GRT) of a rate-controlled oral drug delivery system
reduces inter-subject variability and the so-called “peak and
valley” effect, leading to increased predictability and
bioavailability of the dosage form, especially for molecules
with a narrow absorption window2. Moreover, the total
gastrointestinal transit time is prolonged, thus, the number
of dosage regimen can be reduced and solubility can be
improved for drugs that are less soluble in a high pH
environment. Floating Drug Delivery Systems (FDDS)
first described by Davis (1968), are low-density systems
that have sufficient buoyancy to float over the gastric
contents and remain in the stomach for a prolonged period.
While the system floats over the gastric contents, the
drug is released slowly at the desired rate, which
results in increased gastro-retention time and reduces
 Research J. Pharm. and Tech. 6(12): December 2013
fluctuations in plasma drug concentration. Floating
microspheres are gastroretentive drug delivery systems
based on a non-effervescent approach. Hollow
microspheres, microballoons or floating microparticles are
terms used synonymously for floating microspheres.
Floating microspheres are, in a strict sense, spherical empty
particles without a core. These are free-flowing particles,
with size ranging from 1 to 1000 µm. This gastrointestinal
transit-controlled preparation is designed to float on gastric
juice with a specific density of less than one. This property
results in delayed transit through the stomach. The drug is
released slowly at desired rate, resulting in increased gastric
retention with reduced fluctuations in plasma drug
concentration3. The objective of the present review is to
focus on the method of preparation, and the various
parameters affecting the performance and characterization
of floating microspheres. The present review is a source of
detailed information about the various aspects of floating
microspheres.
Multi-particulate drug delivery systems are mainly oral
dosage forms consisting of a multiplicity of small discrete
units, each exhibiting some desired characteristics. In
these systems, the dosage of the drug substances is
divided on a plurality of subunit, typically consisting of
thousands of spherical particles with diameter of 0.05-
2.00 mm. Thus multi-particulate dosage forms are
pharmaceutical formulations in which the active substance
is present as a number of small independent subunits.
To deliver the recommended total dose, these subunits are
filled into a sachet and encapsulated or compressed into a
tablet. Floating multi-particulate systems include: hollow
microspheres (micro-balloons), low density floating micro-
pellets and floating micro-beads. Hollow microspheres
are in strict sense, spherical empty particles without
core4,5. The term microcapsule is defined as a spherical
particle size 50nm to 5 nm, containing core substance.
Figure 1: Rationale for the use of GRDDS
Basic gastrointestinal tract physiology
Anatomically, the stomach is divided into three regions:
fundus, body, and antrum (pylorus). The proximal part
made of fundus and body acts as a reservoir for un-digested
material, whereas the antrum is the main site for mixing
motions and acts as a pump for gastric emptying, through
propelling actions. Gastric emptying occurs during fasting
as well as in fed states. The pattern of motility is, however,
1453
distinct in the two states. During the fasting state, an
interdigestive series of electrical events takes place, cycling
through both stomach and intestine every two to three
hours. This is called the interdigestive my-loelectric cycle
or migrating myloelectric cycle (MMC), which is further
divided into the following four phases, as described by
Wilson and Washington (1989)6.
1. Phase I (basal phase) lasts from 40 to 60 minutes with
rare contractions.
2. Phase II (preburst phase) lasts for 40 to 60 minutes with
intermittent action potential and contractions. As the phase
progresses, the intensity and frequency also increases
gradually.
3. Phase III (burst phase) lasts for four to six minutes. It
includes intense and regular contractions for a 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.
4. Phase IV lasts for zero to five minutes and occurs
between phases III and I of two 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 the fasted state.
These contractions result in reduced size of food particles
(to less than 1 mm), which are then propelled toward the
pylorus in a suspension form. During the fed state, onset of
MMC is delayed, resulting in slowdown of gastric emptying
rate. Scintigraphic studies determining gastric emptying
rates have revealed that orally administered controlled-
release dosage forms are subject to basically two
complications, namely short gastric residence time and
unpredictable gastric emptying rate7.
Approaches to gastric retention
Over the last three decades, various approaches have been
pursued to increase the retention of an oral dosage form in
the stomach, including floating systems, swelling and
expanding systems, bioadhesive systems, modified-shape
sys-terms, high-density systems, and other delayed gastric
emptying devices8. FDDS or hydrodynamically balanced
systems have a bulk density lower than gastric fluids and
thus 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 a desired rate from the system. After the
release of drug, the residual system is emptied from the
stomach. This results in an increase in the GRT and a better
control of fluctuations in plasma drug concentrations in
some cases. Swelling type dosage forms are such that after
swallowing, these products swell to an extent that prevents
their exit from the stomach through the pylorus. As a result,
the dosage form is retained in the stomach for a long period
of time. These systems may be referred to as ‘plug type
systems’ since they exhibit a tendency to remain lodged at
the pyloric sphincter. Bioadhesive systems are used to
localize a delivery device within the lumen and cavity of the
body to enhance the drug absorption process in a site-
specific manner9.
 Research J. Pharm. and Tech. 6(12): December 2013

Factors affecting gastric retention. 2. Superior to single-unit floating dosage forms, as such
There are several factors that can affect gastric emptying microspheres release drugs uniformly and there is no
(and hence GRT) of an oral dosage form. These factors risk of dose dumping.
include density, size, and shape of dosage form, associated 3. Enhanced absorption of drugs that solubilise only in
intake of food and drugs such as anticholinergic agents stomach.
(e.g., atropine, propantheline), opiates (e.g., codeine) and 4. Site-specific drug delivery to the stomach can be
prokinetic agents (e.g., metoclopramide, cisapride), and achieved.
biological factors such as gender, posture, age, body mass 5. Avoidance of gastric irritation, due to sustained release
index, and disease states (e.g., diabetes, Crohn’s disease). effect.
The rate of gastric emptying depends mainly on viscosity, 6. Better therapeutic effect of short half-life drugs can be
volume and on the caloric content of meals. Nutritive achieved.
density of meals helps determine gastric emptying time.
The prolongation of the GRT by food is expected to Suitable drug candidates for floating drug delivery
maximize drug absorption from a FDDS. This may be system
rationalized in terms of increased dissolution of drug and In general, appropriate candidates for floating drug delivery
longer residence at the most favorable sites of absorption. system are the molecules that have poor colonic absorption
The resting volume of the stomach is 25 to 50 mL. Volume but are characterized by better absorption properties at the
of liquids administered affects gastric emptying time. When upper parts of the GIT [15].
volume is large, emptying is faster. Fluids taken at body 1. Drugs with narrow absorption window in GI tract, e.g.,
temperature leave the stomach faster than colder or warmer Para aminobenzoic acid, furosemide, riboflavin in a
fluids. Studies have revealed that gastric emptying of a vitamin deficiency and Levodopa.
dosage form in the fed state can also be influenced by its 2. Drugs which are primarily absorbed from stomach and
size. Concern regarding the role of food in the prolongation upper part of GIT, e.g., Calcium supplements,
of the GRT has also provided insights into other Chlordiazepoxide and Scinnarazine.
determinants of gastric retention. For instance, studies have 3. Drugs that act locally in the stomach, e.g., Antacids
shown that the GRT of a dosage form in the fed state can and Misoprostol.
also be influenced by its size. Small-size tablets are emptied 4. Drugs that degrade in the colon, e.g., Ranitidine HCl
from the stomach during the digestive phase, while larger- and Metronidazole.
size units are expelled during the housekeeping waves10. In 5. Drugs that disturb normal colonic bacteria, e.g.
order to pass through the pyloric valve into the small Amoxicillin trihydrate.
intestine, particle size should be within the range of 1 to 2
mm6. The pH of the stomach in fasting state is ~1.5 to 2.0
Methods of preparation of hollow microspheres
and, in fed state, it is 2.0 to 6.0. A large volume of water
Hollow microspheres are prepared through the solvent
administered with an oral dosage form raises the pH of diffusion and evaporation method to create the hollow inner
stomach contents above 4. core. The solvent is evaporated either by increasing the
Studies have shown that the gastric residence time can betemperature under pressure or by continuous stirring. Sato
significantly increased under the fed conditions, since the
et al. prepared the floating microspheres by the emulsion
MMC is delayed11. Several formulation parameters can solvent diffusion method, utilizing enteric acrylic polymers
affect gastric residence time. More reliable gastric emptying
dissolved with drug in a mixture of dichloromethane and
ethanol13. The above solution was introduced in the aqueous
patterns are observed for multiparticulate formulations, as
compared to single-unit formulations, which suffer from the
solution of polyvinyl alcohol at 40 ºC with constant stirring
“all or none concept.” As the units of multiparticulate to form an oil-in-water (o/w) emulsion. After agitating the
systems are distributed freely throughout the
system for 1 hour, the resulting polymeric particulate
gastrointestinal tract, their transport is affected to a lesser
systems were sieved between 500 and 1000 mm and then
extent by the transit time of food, when compared to single-
dried overnight at 40ºC to produce hollow microspheres.
unit formulations12. Size and shape of dosage unit also Jain et al. used the emulsion solvent diffusion technique
affect gastric emptying. The density of a dosage form also
with a modification. The drug was adsorbed on a porous
affects the gastric emptying rate. A buoyant dosage form carrier (calcium silicate). The drug-adsorbed porous carrier
having a density of less than that of the gastric fluids will
was added into the polymer solution (Eudragit S) in the
float. Since it is away from the pyloric sphincter, the dosage
mixture of ethanol and dichloromethane (2:1) and sonicated
unit is retained in the stomach for a prolonged period. using a probe sonicator. The resulting suspension was
Posture and nature of the meal also have an effect on gastric
poured into an aqueous solution of polyvinyl alcohol
emptying. (0.75% w/v) at 40 ºC. The emulsion was stirred at 500 rpm
employing a propeller-type agitator for 3 hours. The
Advantages of floating microspheres microspheres were separated by filtration, washed with
1. Bioavailability enhances, despite first pass effect, water and dried at room temperature in the desiccators for
because fluctuations in plasma drug concentration are 24 hours14.
avoided, and a desirable plasma drug concentration is
maintained by continuous drug release.

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 Research J. Pharm. and Tech. 6(12): December 2013

Table 1: List of recently marketed drug formulation utilizing FDDS

Sr. No Dosage Form Drug Polymer Method
1 Multiparticulate FDDS Zolpidem tartarate (Eudragit® NE 30D) Gas generation technique
2 Floatingmicrospheres Cephalexin Ethyl Cellulose (EC) Emulsion solvent evaporation
3 Hollowmicrospheres Ranitidine HCl Eudragit RLPO Solvent evaporation method
4 Floatingmicroparticles Metoprolol Polymethacrylate (Eudragit S100, Non-aqueous emulsion solvent
succinate RSPO, RLPO) evaporation method
5 Drug-loaded beads Pantoprazole Alginate, Sterculia gum Ionotropic gelation
6 Floating matrixtablets Acyclovir Hydroxypropylmethylcellulose Gas generation technique
4000
7 Cinnarizine-loaded Cinnarizine HPMC K4M, HPMCK100M Emulsion-gelation method
EMG beads
8 Floating alginatebeads Levofloxacin Methyl cellulose Gas generation technique
Hemihydrate
9 Floating microspheres Aceclofenac Eudragit RS 100 Emulsification solvent evaporation
technique
10 Floating microspheres Aceclofenac Eudragit S 100 (ES):Eudragit RL Emulsion solvent diffusion technique
100
11 Self-emulsifying Tetrahydrocurcumin Glyceryl behenate andsodium ----
floating pellet starch glycolate
12 Floating matrix tablets Antiretroviral drug Hydroxypropylmethylcellulose Gas generation technique
13 Gas generation Verapamil HCl Carbopol Gas generation technique
technique
14 Sustained-release Metoprololsuccinate Gelucire 43/01 andGelucire 44/14 Melt-solidification technique
matrices
15 Floating matrix tablets Antiretroviraldrug Hydroxypropylmethylcellulose Gas generation technique

Method of preparation of floating microspheres 2. Oil in water emulsion solvent evaporation technique
Wide ranges of developmental techniques are available for In this process, both the drug and the polymer should be
the preparation of Gastro retentive floating microspheres. insoluble in water while a water immiscible solvent is
However, solvent evaporation technique and ionotropic required for the polymer. In this method, the polymer is
gelation method have been extensively employed by large dissolved in an organic solvent such as dichloromethane,
number of scientific investigators worldwide to explore the chloroform, or ethyl acetate, either alone or in
different vistas of floating microspheres. During the combination18. The drug is either dissolved or dispersed into
preparation of floating controlled release microspheres, the polymer solution and this solution containing the drug is
choice of optimal method has utmost relevance for the emulsified into an aqueous phase to make an oil-in water
efficient entrapment of active constituents. Selection of emulsion by using a surfactant or an emulsifying agent.
fabrication technique generally depends upon the nature of After the formation of a stable emulsion, the organic
the polymer, the drug, and their intended use. Characteristic solvent is evaporated either by increasing the temperature
features of materials and the process engineering aspects under pressure or by continuous stirring. Solvent removal
strongly influence the properties of microspheres and the from embryonic microspheres determines the size and
resultant controlled release rate.15,16 morphology of the microspheres. It has been reported that
the rapid removal of solvent from the embryonic
1. Solvent evaporation technique microspheres leads to polymer precipitation at the o/w
This technique is widely employed by large number of interface. This leads to the formation of cavity in
pharmaceutical industries to obtain the controlled release of microspheres, thus making them hollow to impart the
drug17.This approach involves the emulsification of an floating properties.
organic solvent (usually methylene chloride) containing
dissolved polymer and dissolved/dispersed drug in an
excess amount of aqueous continuous phase, with the aid of
an agitator. The concentration of the emulsifier present in
the aqueous phase affects the particle size and shape. When
the desired emulsion droplet size is formed, the stirring rate
is reduced and evaporation of the organic solvent is realized
under atmospheric or reduced pressure at an appropriate
temperature. Subsequent evaporation of the dispersed phase
solvent yields solid polymeric micro particles entrapping
the drug. The solid micro particles are recovered from the Figure 2: Preparation technique (emulsion-solvent diffusion
suspension by filtration, centrifugation, or lyophilisation. method) and mechanism of ‘microballoon’ Formation.
For emulsion solvent evaporation, there are basically two
systems which include oil-in-water (o/w) and water-in-oil 3. Oil in oil emulsification solvent evaporation technique
(w/o) type. This oil-in-oil (sometimes referred as water-in-oil)
emulsification process is also known as non aqueous
emulsification solvent evaporation. In this technique, drug
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 Research J. Pharm. and Tech. 6(12): December 2013
and polymers are co dissolved at room temperature into
polar solvents such as ethanol, dichloromethane,
acetonitrile etc. with vigorous agitation to form uniform
drug–polymer dispersion. This solution is slowly poured
into the dispersion medium consisting of light/heavy liquid
paraffin in the presence of oil soluble surfactant such as
Span. The system is stirred using an overhead propeller
agitator at 500 revolutions per minute (rpm) and room
temperature over a period of 2–3 h to ensure complete
evaporation of the solvent. The liquid paraffin is decanted
and the micro particles are separated by filtration through a
Whitman filter paper, washed thrice with n-hexane, air
dried for 24 h and subsequently stored in desiccators.[33-
37] Span 60 is generally used which is non ionic surfactant.
Span 60 has an HLB value of 4.3 and acts as a droplet
stabilizer and prevents coalescence of the droplets by
localizing at the interface between the dispersed phase and
dispersion medium.19
4. Ionotropic gelation method
In this method, cross linking of the polyelectrolyte takes
place in the presence of counter ions to form gel matrix.
This technique has been generally employed for the
encapsulation of large number of drugs. Polyelectrolyte
such as sodium alginate having a property of coating on the
drug core and acts as release rate retardant contains certain
anions in their chemical structure. These anions forms
meshwork structure by combining with polyvalent cations
and induce gelation. Microspheres are prepared by dropping
drug loaded polymeric solution using syringe into the
aqueous solution of polyvalent cations. The cations diffuses
into the drug loaded polymeric drops, forming a three
dimensional lattice of ionically cross linked moiety.
Microspheres formed left into the original solution for
sufficient time period for internal gelification and they are
separated by filtration. Natural polymers such as alginates
can be used to improve drug entrapment and are widely
used in the development of floating microspheres.20
Figure 03: Ionotropic gelation method
1456
5. Emulsion solvent diffusion method
In this method solution of polymer and drug in ethanol
methylene chloride is poured into an agitated aqueous
solution of poly (vinyl alcohol). The ethanol rapidly
partitions into the external aqueous phase and the polymer
precipitates around methylene chloride droplets. The
subsequent evaporation of the entrapped methylene chloride
leads to the formation of internal cavities within the micro
particles.21
6. Single emulsion technique
In this method, micro particulate carriers of natural
polymers i.e. those of proteins and carbohydrates are
prepared by single emulsion technique. The natural
polymers are dissolved or dispersed in aqueous medium
followed by dispersion in non-aqueous medium like oil
with the help of cross linking agent.22
7. Double emulsion technique
This method involves the formation of the multiple
emulsions or the double emulsion such as w/o/w. This
method can be used with the natural as well as synthetic22.
8. Phase separation coacervation technique
It is based on the principle of decreasing the solubility of
the polymer in organic phase to affect the formation of
polymer rich phase known as co-acervates. The drug
particles are dispersed in a solution of the polymer and an
incompatible polymer is added to the system which makes
first polymer to phase separate and engulf the drug
particles23
9. Polymeriztion technique
The polymerization techniques conventionally used for the
preparation of the microspheres are mainly classified as:
1. Normal Polymerization
It is carried out using different techniques as bulk,
suspension, precipitation, emulsion and micellar
polymerization processes. Bulk polymerization has an
advantage of formation of pure polymers.
2. Interfacial Polymerization
It involves the reaction of various monomers at the interface
between the two immiscible liquid phases to form a film of
polymer that essentially envelops the dispersed.22,23
10. Spray drying and spray congealing
These methods are based on the drying of the mist of the
polymer and drug in the air. The polymer is first dissolved
in a suitable volatile organic solvent such as
dichloromethane, acetone, etc. The drug in the solid form is
then dispersed in the polymer solution under high speed
homogenization. This dispersion is then atomized in a
stream of hot air. The atomization leads to the formation of
the small droplets or the fine mist from which the solvent
evaporates instantaneously leading the formation of the
microspheres in a size range 1-100 µm. Depending upon the
removal of the solvent or cooling of the solution, the two
 Research J. Pharm. and Tech. 6(12): December 2013

processes are named spray drying and spray congealing

respectively.22,23

11. Hot melt encapsulation method

Lin WJ and Kang WW compared the performance of
Percentage of drug entrapment
Indomethacin micro particles and their release properties
The percentage of drug entrapment can be calculated by the
after coating with chitosan and gelatin, respectively. Here
following equation.
the poly (epsilon-caprolactone) (PCL) micro particles were
prepared by the hot-melt encapsulation method. This
method is having a disadvantage that thermo-labile
substances cannot be used24.
Floating behavior
Characterization/evaluation of floating microspheres The floating test on the microspheres is carried out using
Particle size the dissolution method II apparatus, specified in the USP
Size is measured using an optical microscope, and mean XXII. The microspheres are spread over the surface of the
particle size is calculated by measuring 200–300 particles dispersing medium (900 ml), which is agitated by a paddle
with the help of a calibrated ocular micrometer. rotated at 100 rpm. Disintegration test solution No. 1 (pH
1.2), containing Tween 20 (0.02%, w/v), was used as a
Different sizes of microspheres and their distribution in dispersing medium to simulate gastric fluid. After agitation
each batch are measured by sieving in a mechanical shaker, for a previously determined interval, the hollow
using a nest of standard sieves (ASTM) and the shaking microspheres that floated over the surface of medium and
period of 15 minutes. Particle size distribution is those that settled to the bottom of the flask were recovered
determined and the mean particle size of microspheres is separately. After drying, each fraction of the hollow
calculated by using the following formula25. microspheres was weighed. The buoyancy of the hollow
21
Mean particle size = Σ(mean particle size of the fraction× microspheres was represented by the following equation .
weight fraction)/Σ(weight fraction)

Tapped density and compressibility index

The tapping method is used to determine the tapped density
and percentage compressibility index, as follows 26. In vivo buoyancy
The in vivo transit behavior of the floating and non floating
microspheres was monitored using 12 one-year-old male
albino rabbits. These rabbits were divided into two groups,
i.e., group I and group II. In order to standardize the
conditions of GI motility, the animals were fasted for 12
hours prior to the commencement of each experiment.
Floating microspheres (100 mg) were orally administered in
where V and Vo are the volumes of the sample after and suspension form to the animals in group I and non-floating
before the standard tapping, respectively. microspheres were administered to group II, followed by a
sufficient volume of drinking water. The location of the
Surface morphology formulation in the stomach was monitored by keeping the
The external and internal morphology of the microspheres subjects in front of a gamma camera. In between the gamma
is studied by scanning electron microscopy (SEM). scannings, the animals were freed and allowed to move and
carry out normal activities, but were not allowed to ingest
Percent Yield any food or water until the formulation had emptied the
The yield was calculated from the following equation. stomach completely14.

Kawashima et al. (1991) prepared hollow microspheres

Percentage of drug content / drug loading amount(%)
A fixed amount of microspheres containing a drug are
dissolved in a suitable solvent such as ethanol, methanol,
etc. by ultrasonication. The solution is then filtered through
a 5 µm membrane filter. Finally, drug concentration is
determined by the UV, spectrophotometrically. Drug
content is calculated according to following equation:
made with Eudragit S, containing barium sulfate as a
contrast agent for the radiographical in vivo test. The study
was carried out with two healthy male volunteers, free of
detectable gastrointestinal diseases or disorders. Each
subject, having fasted overnight, had a light Japanese
breakfast (one rice ball and one cup of soup). After 30
minutes, each subject ingested two hard-gelatin capsules
packed with hollow microspheres (1000 mg), together with
100 ml of water. The intragastric behavior of the hollow
microspheres after dosing was observed by taking a series
of X-ray photographs at suitable intervals.

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 Research J. Pharm. and Tech. 6(12): December 2013
In vitro release studies 9.
In vitro dissolution studies can be carried out in a USP
paddle type dissolution assembly. Microspheres equivalent
to the drug dose are added to 900 ml of the dissolution 10.
medium and stirred at 100 rpm at 37 ± 0.5 °C. Samples are
withdrawn at a specified time interval and analyzed by any
suitable analytical method, such as UV spectroscopy or 11.
HPLC, etc27.
In vivo studies
In vivo studies are generally conducted in healthy male 12.
albino rabbits weighing 2-2.5 kg. The animals are fasted for
24 hours before the experiments; however, they are given
free access to food and water during the experiments. Blood 13.
samples (2 mL) are collected from the marginal ear vein
into heparinized centrifuge at an appropriate time interval27
CONCLUSION:
Gastro retentive multiparticulates have emerged as an
efficient means of enhancing the bioavailability and
controlled delivery of many drugs. Multiparticulate drug
delivery systems provide several all the advantages
including greater flexibility and adaptability of
microparticulate dosage forms which gives clinicians and
those engaged in product development powerful new tools
to optimize therapy. The increasing sophistication of
delivery technology will ensure the development of
increasing number of gastroretentive drug delivery systems
to optimize the delivery of molecules that exhibit narrow
absorption window, low bioavailability and extensive first
pass metabolism. It is little wonder therefore, that such
systems are growing rapid in popularity. The control of
gastro intestinal transit could be the focus of the next
decade and may result in new therapeutic possibilities with
substantial benefits for patient.
REFERENCES:
1. Hilton, A.K.; Deasy, P.B. In vitro and in vivo evaluation of an
oral sustained-release floating dosage form of amoxycillin
trihydrate. Int. J. Pharm., v.86, 1992:79-88.
2. Groning, r.; heun, g. Oral dosage forms with controlled
gastrointestinal transit. Drug dev. Ind. Pharm., v.10, 1984: 527-
539.
3. Holt, S.; Cervantes, J.; Wilkinson, A.A.; Wallace, J.H.K.
Measurement of gastric emptying rate in humans by real-time
ultrasound. Gastroenterology, v.89, 1985:752-759.
4. Dhole AR, Gaikwad PD, Bankar VH, Pawar SP. A Review on
Floating Multiparticulate Drug Delivery System- A Novel
Approach to Gastric Retention. IJPSRR. 6(2); 2011:205-211.
5. Somwanshi SB, Dolas RT, Nikam VK, Gaware VM, Kotade KB,
Dhamak KB and Khadse AN. Floating Multiparticulate Oral
Sustained Release Drug Delivery System. J.Chem.Pharm Res.
3(1); 2011:536-547.
6. Wilson CG, Washington N. The stomach: its role in oral drug
delivery. In: Rubinstein, MH, editors. Physiological
Pharmaceutical: Biological barriers to drug absorption.
Chichester, U.K.: Ellis Horwood. 1989:47-70.
7. Christmann, V.; Rosenberg, J.; Seega, J.; Lehr, C.M.
Simultaneous in vivo visualization and localization of solid oral
dosage forms in the rat gastrointestinal tract by magnetic
resonance imaging (MRI). Pharm. Res., v.14, 1997:1066-1072.
8. Shah S.H, Patel J.K and Patel N.V. Stomach Specific Floating
Drug Delivery System: A review. Inter. J PharmTech Res. 1(3);
2009:623-633.
1458
El Gamal SS, Naggar VF, Allam AN. Optimization of acyclovir
oral tablets based on gastroretention technology: Factorial design
analysis and physicochemical characterization studies. Drug
Development and Industrial Pharmacy;37(7); 2011:855-67.
Sharma N, Agarwal D, Gupta MK and Khinchi MP. A
Comprehensive Review on Floating Drug Delivery System.
IJRPBS. 2(2); 2011:428-441.
Mojaverian, P.; Ferguson, R.K.; Vlasses, P.H.; Rocci, M.R.J.R.;
Oren, A.; Fix, J. A.; Caldwell, L.J.; Gardner, C. Estimation Of
Gastric Residence Time Of The Heidelberg Capsules In Humans:
Effect Of Varying Food Composition. Gastroenterology, V.89,
1985:392-397.
Bechgaard, H.; Ladefoged, K. Distribution Of Pellets In
Gastrointestinal Tract. The Influence On Transit Time Exerted
By The Density Or Diameter Of Pellets. J. Pharm. Pharmacol.,
V.30; 1978 :690-692,.
Sato, Y.; Kawashima, Y.; Takeuchi, H.; Yamamoto, H. In Vitro
And In Vivo Evaluation Of Riboflavin-Containing Microballoons
For A Floating Controlled Drug Delivery System In Healthy
Humans. Int. J. Pharm.V.275; 2004:97-107.
14. Jain, S.K.; Agrawal, G.P.; Jain, N.K. A Novel Calcium Silicate
Based Microspheres Of Repaglinide: In Vivo Investigations. J.
Control. Release, V.113, P.111-116, 2006
15. Okada H, Toguchi H. Critical Reviews In Therapeutics Drug
Carrier Systems, 12(1); 1995:1-99.
16. Vyas. In: Jain N.K. Pharmaceutical Product Development, CBS
Publishers, New Delhi, 2006:112-138.
17. Li M, Rouaud O, Poncelet D. Microencapsulation by solvent
evaporation: State of the Art for Process Engineering
Approaches, International Journal of Pharmaceutics, 363(1-2);
2008:26-39.
18. Gupta, P.K.; Sau-Hung, S.; Robinson, J. Bioadhesive/
mucoadhesive in drug delivery to the gastrointestinal tract. In:
LENAERTS, V.; GURNEY, R. (Eds.). Bioadhesive drug delivery
system. Boca Raton: CRC Press, 1990: 65-92.
19. Shivakumar HN, Patel R, Desai BG. Formulation optimization of
propranolol hydrochloride microcapsules employing central
composite design. Indian Journal of Pharmaceutical Sciences,
70(3); 2008: 408-413.
20. Ma N, Xu L, Wang Q, Zhang X, Zhang W, Li Y, Jin L, Li S.
Development And Evaluation Of New Sustained-Release
Floating Microspheres. International Journal Of
Pharmaceutics,1(2); , 2008:82-90.
21. Kawashima Y, Niwa T, Takeuchi H, Hino T. Preparation of
multiple unit hollow microspheres (microballoons) with acrylic
resin containing tranilast and their drug release characteristics (in-
vitro) and floating behaviour (in-vivo), J. Con. Rel. 16; 1991:279-
290.
22. Vyas SP, Khar RK. Targeted and Controlled Drug Delivery
Novel Carrier System. New Delhi, CBS Publishers and
Distributors, 2004, pp. 417-457.
23. Alagusundaram M, Madhusudana CC, Umashankari K.
Microspheres as A Novel Drug Delivery Sysytem-A Review,
International Journal of Chemical Technology and Research 1(3);
2009: 526-534.
24. Mathew TS, Devi SG, Prasanth VV, Vinod B. NSAIDs as
Microspheres. The Internet Journal of Pharmacology, 6(1);
2008:101-105.
25. Badri, V.N.; Thomas, P.A.; Pandit, J.K.; Kulkarni, M.G.;
Mashelkar, R.A. Preparation Of Non-Porous Microspheres With
High Entrapment Efficiency Of Proteins By A (Water-In-Oil)-In-
Oil Emulsion Technique. J. Control. Release, V.58; 1999:9-20.
26. Sinko, P.J. Micrometrics. In: Martin, A. (Ed.) Martin’s Physical
Pharmacy And Pharmaceutical Science. 5. Ed. Philadelphia:
Lippincott Willians And Wilkins/A Wolters Kluwer Company,
2006:553-559.
27. Wei, Y.; Zhao, L. In Vitro And In Vivo Evaluation Of Ranitidine
Hydrochloride Loaded Hollow Microspheres In Rabbits. Arch.
Pharm. Res., V.31; 2008:1369-1377.