Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 38-49 [AJPTech.

ISSN- 2231–5705 (Print) www.asianpharmaonline.org

ISSN- 2231–5713 (Online)

RESEARCH ARTICLE

Formulation and evaluation of floating matrix tablet of Losartan for gastro-

retentive drug delivery
B. Ranga Nayakulu1*, Nakka Ravi Kumar1, Ch. Kiran Kumar, P. Raja Abhilash2
1
Srinivasa Institute of Pharmaceutical Sciences, Proddatur, A.P.
2
S.V.S. Group of Institutions, School of Pharmacy, Bhemaram, Hanamkonda,Telangana.
*Corresponding Author E-mail: abhilashmpharm@gmail.com

ABSTRACT:
The prime aim of this research was to develop gastro-retentive delivery system of Losartan which, after oral
administration should have the ability to prolong gastric residence time with desired in vitro release profile.
Losartan was chosen as a model drug because it is poorly absorbed from the lower gastrointestinal tract. The
tablets were prepared by direct compression technique, using various polymers, alone or in combination. The
tablets were evaluated for physical characteristics viz. hardness, friability, weight variation, content uniformity,
and floating capacity. Further, tablets were evaluated for in vitro release characteristics for 12 hr. Among all the
formulations, tablets containing combination of xanthan gum and guar gum showed better floating capacity as
well as sustained release of atenolol at the end of 8 hr. The optimized formulation F4 contains the average
thickness of 2.12, average hardness of 6.7 and friability of 0.44.The F4 formulation which releases the Losartan
in sustained manner in up to 12 hours. The mechanism of release of Losartan from the floating tablets was found
to be diffusion couple with erosion. It was concluded that the tablets prepared by polymer HPMC K4M( 15%)
had efficient floating and sustained release capacity as compared to tablets prepared by using other polymers.

KEY WORDS: Gastro-retentive floating tablets, Losartan, HPMC K100 and Sustained Release.

INTRODUCTION: Among all other above stated approaches floating drug

Oral sustained or controlled drug delivery system is
complicated by restricted gastric residence time. Faster
gastrointestinal transit can prevent complete drug release
in the absorption window zone and reduce the efficacy
dose since the majority of drugs are absorbed in stomach
or the upper part of small intestine [1]. There are a several
approaches that can be used currently to prolong gastric
retention time, such as floating drug delivery systems,
also known as hydrodynamically balanced systems,
swelling and expanding systems, raft system, polymeric
bioadhesive systems, modified-shape systems, high-
density systems, and other delayed gastric emptying
devices [2-4].
Received on 27.04.2015 Accepted on 15.05.2015
© Asian Pharma Press All Right Reserved
Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 59-65
DOI:
59
delivery systems widely used. Floating drug delivery
systems either float due to their low density than
stomach contents or due to the gaseous phase formed
inside the system after they come in contact with the
gastric environment. Based on the mechanism of
buoyancy, two distinctly different technologies i.e. non-
effervescent and effervescent systems have been utilized
in the development of Floating drug delivery systems.
Losartan is an angiotensin-receptor blocker (ARB) that
may be used alone or with other agents to treat
hypertension. Losartan and its longer acting metabolite,
E-3174, lower blood pressure by antagonizing the renin-
angiotensin-aldosterone system (RAAS); they compete
with angiotensin II for binding to the type-1 angiotensin
II receptor (AT1) subtype and prevents the blood
pressure increasing effects of angiotensin II. Unlike
Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 38-49 [AJPTech.]

angiotensin-converting enzyme (ACE) inhibitors, ARBs
do not have the adverse effect of dry cough. Losartan
may be used to treat hypertension, isolated systolic
hypertension, left ventricular hypertrophy and diabetic
nephropathy. It may also be used as an alternative agent
for the treatment of systolic dysfunction, myocardial
infarction, coronary artery disease, and heart failure[5,6].
It belongs to class III is soluble in acidic pH. Losartan
having narrow therapeutic index, poor bioavailability (25
to 35%) and short biological half life (1.5 2hrs) [7,8].
Conventional tablets should be administered 3 to 4 times
to maintain plasma drug concentration. Administration
of Losartan potassium in a floating drug delivery system
would be more desirable for antihypertensive effects by
maintaining the Losartan plasma concentration well
above the minimum effective concentration.
Development of a controlled delivery system for
Losartan would bring many advantages for patients. The
development of oral controlled release formulations for
Losartan is difficult because of in vivo and in vitro
instability. The drug also undergoes from dose dumping
and burst phenomenon (being freely water soluble) when
formulated as controlled or sustained release
formulation.
was mixed with the required quantity of polymers
HPMC K4M or K100M or Ethylcellulose or in
combination, PVP K30 (5%), sodium bicarbonate (10%),
and Microcrystalline (Q.S) in mortar and pastel for 15
min. The powder blend was then lubricated with talc (2.5
mg) and magnesium stearate (2.5 mg) for additional 3
min and prior to the compression; the prepared powder
blend was evaluated for several tests as mentioned
below. The powder blend was then compressed into
tablets manually on single punch tablet punching
machine using 6 mm standard flat punch.
Evaluation of powder blend
Bulk density and tapped density
Both poured bulk and tapped bulk densities were
determined, by a quantity (3 g) of granules from each
formula, previously lightly shaken to break any
agglomerates formed, was introduced into a 10 mL
measuring cylinder. After the initial volume was
observed, the cylinder allowed tofall under its own
weight onto a hard surface from the height of 2.5 cm at 2
sec intervals. The tapping was continued until no further
change in the volume was noted. The value of bulk
density and tapped density were calculated by using
equation:

The aim of the present work is to develop floating drug Bulk density = M / V0
delivery system for Losartan potassium, which increases Where M= mass of the powder; V0=bulk volume of the
the gastric residence time. The prepared tablets were powder.
evaluated for physical characteristics such as hardness,
weight variation, and drug content uniformity. All the Tapped density = M / Vr
tablets were evaluated for in vitro release characteristics. Where M = mass of the powder, Vr = final tapping
volume of the powder.
EXPERIMENTAL WORK:
Materials and Method Compressibility index
Losartan potassium was obtained as a gift sample from The Carr’s compressibility index and Hausner’s ratio
Torrent Pharmaceuticals Ltd, Ahmadabad. Hydroxy were calculated from the values of bulk density and
Propryl Methyl Cellulose (HPMC), K4M, K100M, Ethyl tapped density.
cellulose, Talc, sodium bicarbonate, magnesium sterate,
Microcrystalline and talc were obtained from CDH (P)
Ltd, New Delhi.

Floating matrix tablet of Losartan potassium were

prepared by direct compression method according to the
formula given in Table 1. Losartan potassium (100 mg)
Table 1: Composition of Floating Tablets of Losartan
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Losartan(mg) 100 100 100 100 100 100 100 100 100
HPMC K4M(%) 10 -- -- 15 -- -- 10 15 15
HPMC K100M(%) -- 10 -- -- 15 -- 10 10 15
EC (%) -- -- 10 -- -- 15 -- -- --
PVP K30 (%) 5 5 5 5 5 5 5 5 5
Sodium bicarbonate(%) 10 10 10 10 10 10 10 10 10
Talc (%) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
Magnesium stearate(%) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
MCC(mg) Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S
Total weight (mg) 200 200 200 200 200 200 200 200 200

60
Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 38-49 [AJPTech.]

Evaluation of tablet VIS spectrophotometer. The content of drug was

Prepared tablet were evaluated for quality control tests calculated using equation generated from calibration
like weight variation test, hardness test, friability test, curve. The test was performed in triplicate and the mean
content uniformity study, and in vitro release study. value was used to construct the release profile.

Weight variation test Determination of release kinetics and release

To study weight variation, tablets from each formulation mechanism
were selected at random and average weight was The rate and mechanism of release of atenolol from the
determined using an electronic balance. Then individual prepared floating tablets were analyzed by fitting the
tablets were weighed and the individual weight was dissolution data into following equations:
compared with an average weight. Weight values were
reported in mg. Mean and SD were calculated. Zero order: C = K0 t
where, K0 is zero-order rate constant expressed in units
Hardness test of concentration/time and t is the time.
For each formulation, the hardness of six tablets was
determined using a hardness tester (Monsento, Mumbai, First Order: LogC = LogC0 - K1 t / 2.303
India). Hardness values were reported in kg/cm2. Mean
and SD were calculated. where, C0 is the initial concentration of drug and K1 is
first order constant.
Friability test
For each formulation, six tablets were weighed. The To describe the drug release behavior from polymeric
tablets were placed in a Roche friabilator (Labotech, systems, the dissolution data were also fitted according
Mumbai, India) and subjected to 100 rotations in 4 min. to the well-known exponential Korsmeyer-Peppas
The tablets were then dedusted and reweighed. The equation.
friability was calculated as the percent weight loss.
Mt / M∞ = Ktn
Drug content uniformity study
Five tablets were weighed individually, then placed in a where Mt / M∞ is fraction of drug released at time t, K is
mortar and powdered with a pestle. An amount the release rate constant incorporating structural and
equivalent to 25 mg drug (100 mg) was extracted with geometric characteristics of the tablet, and n is the
100 mL of 0.1M HCl (pH 1.2), stirred for 15min using release exponent.
magnetic stirrer (Labotech, Mumbai, India). The solution
was filtered through a filter (0.22 μm pore size), properly RESULTS AND DISCUSSION:
diluted with 0.1 M hydrochloric acid and the drug Losartan floating tablets were prepared by using HPMC
content was measured using UV-VIS spectrophotometer K4M orK100M or Ethylcellulose or in combination as a
at 234 nm. polymeric retardant materials and sodium bicarbonate as
gas forming agent to float the tablets in stomach. Carbon
Buoyancy study dioxide which is formed by combination of citric acid
The in vitro buoyancy was characterized by floating lag with sodium bicarbonate is just entrapped by the
time and total floating time. The test was performed polymer and decreases the density of tablet below the
using USP 24 type II apparatus (Timestan, Kolkata, density of gastric fluid which results in floating of the
India) at 100 rpm in 900 mL of 0.1M HCl (pH 1.2) tablet.
maintained at 37±0.5°C. The time required for tablet to
rise to the surface of dissolution medium and duration of The micromeritics parameters of the powder blend of
time the tablet constantly float on dissolution medium different formulation batches are shown in Table 2.
were noted as floating lag time and total floating time, Angle of repose and compressibility index was found to
respectively (n = 3)21 be in the range of 26.1 to 29.6 and 13.16 to 17.78,
respectively. The bulk density and tapped density of the
In vitro drug release study. prepared powder blend was found to be in the range of
The in vitro drug release study was performed using 0.31 to 0.37gm/cm3 and 0.37to 10.45gm/cm3,
USP 24 type II apparatus at 50 rpm in 900 mL of 0.1M respectively. The result of angle of repose indicates good
HCl (pH 1.2) maintained at 37±0.5°C. The samples were flow property of the granules and the value of
withdrawn at predetermined time intervals for period of compressibility index further support for the good flow
8 hr and replaced with the fresh medium. The samples property.
were filtered through 0.45 μm membrane filter, suitably
diluted and analyzed at 234 nm using double beam UV-

61
Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 38-49 [AJPTech.]

Table 2: Micromeritics properties of powder blend of different formulations

Formulations Angle of Repose (θ) Loose Bulk Tapped Bulk %Compressibility Hausner’s ratio
Density (g/ml) Density (g/ml)
F1 26.1 0.37 0.45 17.78 1.22
F2 25.7 0.33 0.38 13.16 1.15
F3 27.4 0.32 0.37 13.51 1.16
F4 27.3 0.38 0.44 13.64 1.16
F5 29.6 0.31 0.37 16.22 1.19
F6 28.4 0.37 0.45 17.78 1.22
F7 27.1 0.32 0.37 13.51 1.16
F8 26.7 0.33 0.38 13.16 1.15
F9 26.3 0.38 0.44 13.64 1.16

The tablets of all formulations was found to be off white, result they are not floated. Whereas, all the other
smooth, flat faced circular with no visible cracks. The formulations shows appreciable floating lag time less
physicochemical properties of all the formulations are than 6 min. Table 4 shows formulations F4, F7, and F8
shown in Table 3. The hardness of the tablets was are able to float above the dissolution medium for more
measured by Monsento hardness tester and was found in than 12hr, which is our desired goal.
between 6.2 to 6.6 kg/cm2. The friability was measured
by Roche friabilator and was found to be within Table 4:Buoyancy properties of the tablets of different
acceptable range i.e. 0.39 to 0.48. The weight variation formulations
Formulations Lag Time Floating time
of the tablet formulations was found to be in the range of 6 min 5hrs
199 to 204 mg, which reflects good uniformity in drug F2 3min 3hrs
content among different formulations. All the F3 20 min 6hrs
formulations showed values within the prescribed limits F4 7 min >12hrs
for tests like hardness, friability and weight variation F5 5 min 6hrs
F6 6 min 8hrs
which indicate that the prepared tablets are of standard F7 3 min >12hrs
quality. F8 4 min >12hrs
F9 6 min 5hrs
Table 3: Post compression parameters of different formulations
Formu Weight Hardness Thickness Friability
lations variation (mm) (%)
The in vitro release profile of the different formulations
F1 200 6.6 2.17 0.39 is shown in Figure 1. The release profile of different
F2 199 6.4 2.37 0.42 formulations shows that S1 and S4 released the whole
F3 201 6.2 2.55 0.40 drug within 6 h. Formulation S2, S3, S5, S6 and S7
F4 202 6.7 2.12 0.44 released the drug within the range of 70-80 % within the
F5 202 6.4 2.38 0.48
time of 8 h. Whereas, formulation S2, S3, S5 and S6
F6 200 6.6 2.19 0.43
F7 201 6.5 2.54 0.42 shows burst release of drug. The formulation S7 released
F8 204 6.4 2.51 0.41 the drug in the same manner of theoretical release profile
F9 203 6.3 2.48 0.44 as calculated using Robinson Erickson equation.

It was observed that formulation F3 and F4 unable to

hold the carbon dioxide within the tablet matrix as a

In-Vitro Drug Release Studies for Floating tablets:

Table 5: Dissolution studies of different formulations
Time(hrs) F1 F2 F3 F4 F5 F6 F7 F8 F9
Dissolution medium 0.1N HCL
1 34.5 43.7 30.3 34.2 24.5 18.2 24.5 18.2 16.2
2 42.7 71.5 44.5 39.4 47.8 23.5 32.4 23.5 22.8
6.8pH phosphate buffer
3 52.9 80.3 66.8 48.1 60.2 30.6 44.2 28.8 38.4
4 69.4 98.4 71.4 54.7 77.3 44.2 54.7 32.6 46.2
5 87.2 - 84.1 64.9 84.5 68.1 64.9 39.2 49.2
6 95.8 - 96.8 82.4 97.6 89.3 75.4 65.5 52.8
8 - - - 92.1 - 97.7 82.1 71.3 68

62
Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 38-49 [AJPTech.]

Fig No 1- Dissolution graph for Floating layer formulations

KINETIC RELEASE MODELS:

Table 6: Release kinetics for F4 formulation for Floating layer
ZERO FIRST HIGUCHI PEPPAS
% CDR Vs T Log % Remain Vs T %CDR Vs √T Log C Vs Log T
Slope 7.786831683 -0.15891117 30.10021941 2.310046705
Intercept 21.71554455 2.135240217 -0.08296857 -0.19489949
Correlation 0.930561471 -0.97385361 0.985152619 0.879950588
2
R 0.865944651 0.948390861 0.970525683 0.774313037

SUMMARY AND CONCLUSION: The prepared dry mixer for floating tablets were also
The Floating tablets containing Losartan were maintained the physiochemical properties of tablets such
successfully prepared by direct compression method. as thickness, hardness, weight variation, friability. The
optimized formulation F4 contains the average thickness
The physiochemical evaluation results for the powdered of 2.12average hardness of 6.7, friability of 0.44.
blend of all trials pass the official limits in angle of
repose, compressibility index. The F4 formulation which releases the Losartan in
sustained manner in up to 12 hours.

63
Asian J. Pharm. Tech. 2016; Vol. 6: Issue 2, Pg 38-49 [AJPTech.]

Hence it may be summarized that the tablets prepared by

direct compression method for floating tablets might be a
perfect and effective formulation to treat the
Hypertension.

REFERENCES:
1. Robinson Jr and Lee V.H.L. Controlled drug delivery:
Fundamentals and Applications. Marcel Dekker, New York.1998.
2. Chein Y.W, Novel Drug Delivery Systems, Marcel Dekker; New
York 1992.
3. Dave BS, Amin AF, Patel MM. Gastro retentive Drug Delivery
System of Ranitidine Hydrochloride: Formulation and In Vitro
Evaluation. AAPS PharmSciTech. 5(2); 2004:34-39.
4. Dalavi V.V. and Patel J. S. Gastro retentive drug delivery system
of an antiretroviral agent. International Journal of Pharm
Tech Research. 1(4); 2009:1678-1684.
5. M. Sivabalan, T Punitha Vani, Phaneendhar Reddy, Vasudevaiah,
Anup Jose and G Nigila. Formulation and evaluation of gastro
retentive Glipizide floating tablets. International Journal of
Comprehensive Pharmacy. 1(3); 2011: 82-87.
6. Sunil K. Jain Govind P. Agrawal and Narendra K. Jain Evaluation
of Porous Carrier-based Floating Orlistat Microspheres for Gastric
Delivery AAPS PharmSciTech. 7(4);2006:49-55.
7. S. B. Bhise and N. H. Aloorkar. Formulation and in vitro
Evaluation of Floating Capsules of Theophylline. Indian Journal of
Pharmaceutical Sciences. 70(2); 2008: 224–227.
8. Vishal G. Karkhile, Manish A. Sontakke, Ritesh R. Karmarkar,
S.D. Barhate and S.V. Tupkari. Formulation and in vitro
evaluation of Furosemide tablets. International Journal of
Pharmaceutical Research and Development. 1(3); 2010 : 224-229.

64