Bilayer Floating Tablet: A Novel
Pharmaceutical Approaches for
Deepika Joshi1*, Kamal Kaushik1,Bhavana Singh1, Nidhi Semwal1
1School of Pharmaceutical Sciences, SGRR University, Dehradun, 248001, India
Submission: September 1, 2021; Published: September 27, 2021
*Corresponding author: Deepika Joshi, Assistant Professor, School of Pharmaceutical Sciences, SGRRU, Dehradun, 248009, India
How to cite this article: Deepika J, Kamal K, Bhavana S, Nidhi S. Bilayer Floating Tablet: A Novel Pharmaceutical Approaches for Gastroretention. Nov Appro Drug Des Dev. 2021; 6(2): 555683. DOI: 10.19080/NAPDD.2021.06.555683
Bilayer floating tablet is a gastro retentive novel delivery system developed for controlled release formulation. This review deals with study upon updated literatures on bilayer floating drug delivery system, its advantages and disadvantages, concept of gastroretention, rationale for drug selection, pharmacokinetic aspect, mechanism, approaches, list of polymers and other ingredients used, in-vitro and in-vivo evaluation, literature survey, marketed products. Incorporation of drugs in bilayer floating tablet remain in gastric region for several hours would significantly prolongs the gastric residence time of drug thereby improving bioavailability/solubility of drugs. This approach may be extensively used to improve therapy with several narrow absorption windows drugs.
Keywords: Gastric retention; Bilayer floating tablet; Stomach; Residence time; Gastric; Controlled drug delivery system
Bilayer tablet are multilayer tablets used in controlled drug delivery system. Bilayer floating tablets consisting of two layer i.e., immediate release layer which releases initial dose from system while the another sustained release layer absorbs gastric fluid (Figure 1), forming an impermeable colloidal gel barrier on its surface and maintain a bulk density of less than unity and thereby it remain buoyant in the stomach . The immediate release layer is comprised of gas generating system i.e., sodium bicarbonate and citric acid control release layer comprised of low density release retardant polymers like HPMC K4M, K15M, E50LV. Bilayer floating tablets can be primary option to avoid chemical in compatibility between active pharmaceutical ingredients by physical separation and to unable the development of different drug relief profile [2,3].
Floating drug delivery system are low density system and having bulk density less than gastric fluid and remain they have sufficiently buoyancy to float over the gastric contents and remain buoyants in the stomach without affecting the gastric emptying rate for a longer period of time . The increase in gastric retention time and a better control of the fluctuations in plasma drug concentrations can be seen. While the system is floating on the gastric content the drug is released slowly at the desire rate reliably buoyant on the surface of the meal. Many buoyant systems developed based on the granules, powder, capsules, tablets, laminated films and hallow microsphere.  Flotation of drug is achieve by in cooperating floating chamber filled with vaccum, air or inert –gas from the system. After release of drug, residual is emptying from the stomach.
The main function of the stomach is to process and transport food.it serve as a short-term storage reservoir, allowing a rather large meal to be consumed quickly. The metabolism of enzymes is promoted in stomach of proteins. The peristalsis of stomach mixes up and grind consumed food with secretions of the stomach, turning food in liquid form. The liquefied bulk is transported to the small intestine for further digestion.  The human anatomy categorizes stomach (Figure 2) in three main parts: fundus, body and antrum (pylorus) .
Fundus: the upper part of the stomach, which forms a bulge above the level of the opening of the oesophagus (furthest from the pylorus).
Body: below the fundus is the body, the main part of the
stomach. The wider end of the funnel, the pyrolicantrum, connects
to the body of the stomach.
Antrum: Provides for the main site for mixing motions and
acts as gastric emptying pump by propeller actions. Both the
fasting and fed states cause gastric emptying .
The proximal portion referred to as fundus and the body
functions as storage for undigested food.
In this phenomenon, series of electric events takes pace in
cycle via stomach and intestine every 2 to 3 hours. There occurs
a phenomenon of inter digestive myloelectric cycle or migrating
myloelectric cycle (MMC) and is divided into 4 phases:
Phase 1- Basal phase, last from 30 to 60 minutes with rate
contractions and is characterized by a lack of secretory, electrical,
and contractile activity.
Phase2- Preburst phase, lasts for 20 to 40min with
intermittent contractions, during which contractile motions
increase in frequency and size.
Phase 3- Burst phase, last for 10 to 20mins with intense and
regular concentrations for shorts periods, termed housekeeper
waves that sweep off undigested food.
Phase 4- Lasts from 0 to 5 minutes and is the transition
periods between phases 3 and 1.
Upon food being ingested, the stomach motions vary fasted to
fed state. It termed as digestive motility pattern and constituted
regular peristalsis as in phases 2 of the states of fast. It reduces
food size (<1mm) propelling food towards pylorus .
a) Density: Dosage form with lower density in the gastric
content can float to the surface while high-density sink to the
bottom of the stomach. Suitable density required for floating
property is less than 1.0gm/cm3.
b) Nature of meal: High amount of fatty acid and other
indigestible polymer slow down the gastric retention time (GRT )
due to variation in gastric motility.
c) Frequency of feed: Gastric retention time can rise by
over 400minutes, when consecutive meals are given related with
a single meal because of the low frequency of MMC.
d) Disease state: Gastric disease such as diabetes, chron’s
disease, hypothyroidism, hyperthyroidism, duodenal ulcer etc
fluctuates the GRT.
e) Size: Size should be more than 7.5mm in diameter to
have improved GRT.
f) Shape: Either round or spherical shaped dosage from
exhibit better property related to other shapes.
g) Single or multiple unit formulation: Multiple unit
formulations show a more expectable release profile and
insignificant damaging of performance because of failure of units,
allow co-administrations of units that have dissimilar release
profiles related with single unit dosage forms.
a) To control the delivery rate of either single or two
different active pharmaceutical ingredients.
b) To modify the total surface area available API layer either
by imposing with one or two inactive layers in order to achieve
swellable /erodible for modified release.
c) T separate incompatible active pharmaceutical indigents
from each other, to control the release of API from one layer by
utilizing the functional property of other layer (such as osmotic
d) For the administration of fixed dose combination of drug,
prolong the product life cycle, buccal/mucoadhesive delivery
systems, fabricate drug delivery system such a chewing device
and floating tablets for gastroretentive drug delivery systems .
A. Osmotic-controlled release oral delivery system
In this technology the system is comprised of two or three
layers among which one or more layer is of drug and other layer
consist of push layer. The drug layer consists of poorly soluble
drug along with diluents having low molecular weight polymer,
suspending agent and osmotic agents. The push layer is of higher
molecular weight osmopolymer and an osmogents. A semipermeable
membrane surrounds the tablet core and is interposed
with an osmotic agent that swells in presence of water. Laser is
used to drill a tiny hole through the membrane. In the stomach,
water passes through the membrane into the pill, causing the
osmotic material to swell, that pushes the drug out of the whole.
The drug is delivered to the body at a constant rate. The product
manufactured using this technology is Glucotrol XI and Procardia
B. Elan drug technology
DUREDASTM or Dual Release Drug Absorption System using
by layer tableting technology, which has been developed to
provide two different release rates from a single dosage form. In
this the tablet are prepared by two separate direct compression
steps that combined and immediate release granulate and a
controlled-release hydrophilic matrix complex with in one tablet.
The immediate release layer, release the drug immediately after
going into the GIT and the controlled release matrix remain intact
and slowly absorbs fluid from the GI tract, which is return causes
the matrix to expand and transform the hydrophilic polymer into
a porous, discuss gel that’s a serves as a barriers between the drug
and fluid and the gel continue to expand, the fluid penetrates into
the dosage form, dissolving the drug and allowing the solution to
diffuse out . The immediate release and controlled release
combination of two drugs are feasible.
C. PRODAS or programmable oral drug absorption
It is a multi-particulate drug delivery technology based on the
encapsulation of controlled release mini tablets in the size of 1.5
to 4mm in diameter this technology can be used to pre programme
the release rate of a drug.it is possible to incorporate different
mini tablet at difference sites within the GIT. This represents a
combination of multi-particulate and hydrophilic matrix tablet
technology and provide the benefit of both system in one dosage
form. Such combination includes immediate release, delayed
release, and controlled release minitablet.
D. Rotab bilayer
RoTab bilayer when using is switched to production mode.
Dose and compression force is automatically regulated by
adjusting filling speed and die table. Hardness is also regulated
when its required .
Polymer and other excipients used for formulation of bilayer
The polymer used for coating or fabrication of bilayer tablets
are hydroxypropyl methyl cellulose (HPMC 1000, HPMC 4000,
HPMC K15, HPMC K4,); beta cyclodextrin, sodium alginate,
hydroxypropyl cellulose (HPC-H, HPC-M), Eudagrit S, Metolose
S.M.100, polyvinylpyrrolidone (PVP), acrylic polymer and
Inert fatty materials: Beewax, Fatty acids, long chain fatty
alcohols, gelucires 39/01 and 43/01.
c) Buoyancy increasing agents (upto 80%) Eg: Ethyl
d) Low density material: Polypripylene foam powder
Pharmacokinetic aspect of bilayer floating tablets
a) Absorption window
He candidates for GRDDS are molecules that have poor colonic
absorption but are characterized by better absorption properties
at upper part of GIT.
b) Enhance bioavailability
The compound having narrow absorption window having
the possibility of continuous administration of the compound at
c) Enhance first pass biotransformation
The pre-systemic metabolism of the tested compound is
increased. When the drug is presented to metabolic enzyme
(cytochrome p-450) in a sustained manner.
d) Improve bioavailability due to reduced
p-glycoprotein activity in 16he duodenum
The drug that P-gp substrate do not undergoes oxidative
metabolism GRDDS may elevate absorption compaired to
immediate and CR dosage form.
e) Reduce frequency of dosing
For drugs with relatively short biological half-life. Sustained
and slow input from GRDDS results flip-flop pharmacokinetic and
enable reduced dosing frequency.
f) Targeted therapy for local elements in upper GIT
The prolonged and sustained administration of the drug from
GRDDS to the stomach may produce local therapy in the stomach
and small intestine.
Pharmacodynamic aspect of bilayer floating tablet
a) Reduce fluctuation of drug concentration.
b) Are associated with peak concentration can be prevented.
Improved selectively in receptor activation.
c) Reduce counter activity of the body.
d) Slow input of drug into the body was shown to minimize
the counter activity leading to higher drug efficiency.
e) Minimize adverse activity of colon- The
pharmacodynamics aspect provides the rationale for GRDDS
formulation for beta-lactumantibiotics that are only absorbed
from the small intestine and due to presence at colon it develop of
microorganism is resistance.
Evaluation techniques of bilayer floating tablets
Vitro evaluation: In this technique the evaluation was done to access the physiochemical properties and release characteristic of the formulation.
A. Pre-compression parameter
i. Angle of repose: With the help of angle of repose, we
can estimate the frictional force in powder. It can be defined as
the maximum angle formed between surface pile of powder and
horizontal plane i.e., height. We can find out the angle of repose by
using the formula.
Where, θ=angle of repose h=height of pile
r= radius of pile29.
The relationship between angle of repose and powder flow is
follows in table:
ii. Compressibility index: The propensity of the powder
to be compressed is estimated by compressibility index and it also
help in measurement of settling and interparticulate interaction
Compressibility index (%) = pt-p0*100/pt
Where pt = trapped density gram/ml
Po= Bulk density gram/ml
iii. Bulk density
It is defined as the ratio of mass of powder to bulk volume.
in this 50cm3 of powder is passed through sieve no.20 than this
introduces in 100ml graduated cylinder .
iv. Tapped density
The increase in bulk density attained after mechanical tapping
in measuring cylinder is called tapped density .
Tapped density= weight of powder taken/tapped volume
v. Hausner ratio
The hausner ratio is the no. that is related to flowability of
powder material. Hausner ratio = tapped density/bulk density
Hausner ratio = Vo/Vf
Where, V0= unsettled apparent volume Vf = Final tapped
vi. Particle size distribution
Sieving method is used to determine particle size distribution.
B. Post-compression parameters
i. Tablets thickness: Three tablets are randomly taken
and then their thickness and diameter are measured by vernier
caliper or by using calibrated screw gauze.
ii. Weight variation test: Twenty tablets are selected
and weight individually. Then the average weight and standard
deviation is calculated. Test passes when not more than two
tablets deviate from average weight. In all formulation, the tablet
weight was more than 324mg, hence 5% maximum difference
iii. Hardness: Hardness indicates the ability of a tablet to
withstand mechanical shock while handling . It is expressed in
kg/cm2 and checked using Monsanto hardness tester by randomly
picking three tablets . In all the cases, mean of five replicate
determinations were taken.
iv. Friability test: This was determined by weighing 26
tablets after dusting, placing them in the roche friabilator and
rotating the plastic cylinder vertically at 25 rpm for 4 min .
After dusting, the total left weight of the tablet was recorded, and
percent friability was calculated by formula:
% Friability= intial wt of tablets- final wt of tablets/initial
weight of tablet × 100
Acceptance limit: % Friability of tablets less than 1 % are
considered acceptable .
v. Disintegration time: One tablet is placed in
disintegration apparatus containing buffer 0.1N HCl or PBS pH 6.8
and test is carried out at 37 °C .
vi. Dissolution studies: It is performed using USP paddle
apparatus at 50 rpm rotational speed maintained at 37°C. At
different time interval 5ml samples is withdrawn and is replaced
with same amount of buffer .
vii. Floating lag time: It is basically the time interval of tablet
to starting floating. It should be less than 1min. It is measured by
the dissolution test apparatus containing 0.1N HCl (900ml).
viii. Floating time: It is the total time taken by tablets that
remains floating in the media .
ix. Drug content uniformity: 10 tablets are taken
and powdered equivalent weight of drug dose is taken and
is transferred to volumetric flask then buffer is added, and
absorbance is determined using UV spectrophotometer .
C. In vivo evaluation of bilayer floating tablets:
i. Radiology: X-ray is widely used for examination of
internal body systems. Barium sulphate is widely used Radio
Opaque Marker. So, BaSO4 is incorporated inside dosage form
and x-ray images are taken at various intervals to view gastric
ii. Scintigraphy: It is similar to x-ray, emitting materials
are incorporated inter dosage form and then images are taken by
scintigraphy. A widely used emitting material is 99Tc.
iii. Gastroscopy: Gastroscopy is peroral endoscopy used
with fiber optic or video systems. Majorly gastroscopy is used to
inspect visually the effect of prolongation in stomach. It can also
provide the detail information of evaluation of GRDDS.
iv. Magnetic marker monitoring: In this technique,
dosage form is magnetically marked with incorporating iron
powder inside, and image is taken by very sensitive bio-magnetic
v. Ultrasonography: It is not used generally because it is
not traceable at intestine.
vi. C13 octanoic acid breath test: C13 Octanoic acid is
absorbed into GRDDS where it undergoes chemical reaction and
liberates CO2 gas. The important carbon atom which will come in
CO2 is replaced with C13 isotope. So, time up to which C1302 gas is
observed in breath can be considered as gastric retention time of
dosage form. As the dosage form moves to intestine, there is no
reaction and no CO2 release. So, this method is cheaper than other
Bilayer tablets are suitable for the sequential release of two
drugs to be given combined. It separates the two mismatching
drugs. The sustained-released tablets whose one layer provides
instant drug release as the initial loading dose while the second
layer is containing the sustained dose. Bilayer tablets are latest
technology that helps in overcoming the limitations of a singlelayered
tablet. Bilayer tablets help in the combined delivery of two
different drugs that have different release profiles. Bilayer tablets
are utilized to administer fix dosage containing different APIs.
They are employed to increase and modify the surface area for
active pharmaceutical ingredients by erodible barriers for custom
A). Herbal bilayer floating tablets
Bilayer floating tablet is the best option for herbal drug
delivery. It could release drug upto 12-24 hours. It improves the
therapeutic effect of drug.
Some of the herbal drugs that can be delivered as bilayer
floating tablets are:
i. Forskolin: It is used as anti-obesity agent reducing fat in
body muscles. It may enhance fat loss without loss of muscle mass.
ii. Black myrobalan: It shows uniform anti-bacterial
activity against ten clinical strains of H.pylori.
iii. Ginger root: It is used for the treatment of gastrointestinal
ailments such as motion sickness, dyspepsia and hyperemesis
gravidarum and it also have chemopreventative activity in animal
iv. Turmeric: It prevents gastric and colon cancers in
v. Berberine: It shows variety of activity against bacteria,
viruses, fungi, protozoans, and helminthes .
B). Treatment of diseases
i. Hypertension and angina pectoris
Nifedipine is a calcium channel blocker of the di-hydropyridine
type which is mainly used for the treatment of hypertension
and angina pectoris. Nifedipine is a suitable candidate for CR
administration due to its short elimination half-life of 2-hrs, its
rapid and complete drug absorption over the entire gastrointestinal
tract, despite its low water solubility and the relationship between
drug plasma concentration and blood pressure reduction [32,33].
Controlled release formulation of nifedipine would be effective
in overcoming the dissolution limitation by slowly supplying the
drug from the intact matrix base during its sojoum in the gastrointestinal
tract and its thus expected to decrease side effect
and improve patient compliance. Control release tablet for oral
administration designed to deliver the drug at gastric region for
treatment of hypertension .
ii. Cardiovascular disease: Atorvastatin immediate
release and aspirin pulsatile release for the treatment of
cardiovascular diseases. Four formulations were prepared
for immediate release layer of atorvastatin using different
concentrations of microcrystalline cellulose and talc by different
compression method [35-37].
iii. Peptic ulcer: The major target of bilayer tablet is to
decrease the pain and promotes ulcer healing, prevention of
C). Targeted drug delivery system
It is the method of delivering medications to the patients
in the manner that increases the concentration of medication
in some part of body related to other. The aim of targeted drug
delivery system is to prolong, localize, target and have protected
drug interaction with the diseased tissue. It reduces the frequency
of dosage taken by patient. There are different types of drug
delivery route such as polymeric micelles, liposomes, lipoproteinbased
drug carrier, nano-particle drug carrier, dendrimers, etc. It
is also used to treat cardiovascular disease and diabetes. The most
important application is to treat cancerous tumours [38-40].
D). Controlled drug delivery system
It aims at releasing the dose of therapeutic directly in the
desired zone during the required period of time. It allows the
maximizing the efficacy of the therapeutic and minimizing e side
effects. For floating drug delivery system, the polymers used must
be highly swellable in shortest time . The control release
matrix tablet containing uniform mixture of drug, polymer and
excipients including gas–generating agents. Nifedipine was mixed
using variable amount of Carbopol p 934 and HPMC (K4M, K15M)
properly in a mortar with weighed number of excipients. The well
will mix powder was compressed by direct compression technique
and used as controlled release layer [42,43].
Drug release is the major area in the pharmaceutical research
work. Through floating bilayer tablets both type of release i.e.,
sustained as well as immediate release can be obtained, and
sustained release can be increased up to 24 hours. It is also
beneficial in providing gastric retention thereby increasing gastric
emptying time as well as increasing bioavailability. Another
advantage is that two drugs can be administrated concurrently at
the same time, which provides better patient compliance. Drugs
with narrow absorption window such as antiviral, antibiotic and
antifungal stand out as better candidate for floating bilayer dosage
form. In the last decade, interest in developing a combination of
two or more active pharmaceutical ingredients (API) in a single
dosage form (bilayer tablet) have increased in the pharmaceutical
industry, promoting patient convenience and compliance. Due to
the use of different materials and complex geometric boundaries
between adjacent layers, the mechanical structures of this
drug delivery system have become quite intricate, requiring
complicated tablet architectures as well as patient friendly. Gastro
retentive drug delivery system prolongs the retention time of
dosage forms in the stomach or upper gastro-intestinal tract, as
to improve solubility, bioavailability and the therapeutic efficacy
of the drugs. Several pharmaceutical companies are currently
developing bilayer tablets. For a variety of reasons: patients’
extension, therapeutic marketing to name a few.
Bilayer tablet is improved beneficial technology to overcome
the shortcoming of single layered tablet. Bilayer tablets provide
one of the important design approaches where incompatible
drugs, with different indication, and same drug with different
release rate can be incorporated in a single unit. Bilayer tablet is
suitable for sequential release of one or two drugs in combination,
separate two incompatible substances and also for sustained
release tablet in which one layer is immediate release as initial
dose and second layer is maintenance dose. The preparation of
tablets in the form of bilayer is used to provide systems for the
administration of drugs, which are incompatible and provide
controlled release tablet preparations by providing surroundings
or multiple swelling layers.
All authors have contributed significantly in the preparation
of the manuscript and are in agreement with the content of the
manuscript and agree to submission to Novel Approaches in Drug
Designing & Development.The authors express gratitude to School
of Pharmaceutical Sciences, SGRR University, Dehradun.
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