Objective: The purpose of the present research investigation was to formulate sustained release (SR) formulations for
losartan potassium using 32
factorial designs. Methods: Losartan potassium is an antihypertensive agent, non-peptide
angiotensin-II receptor (type AT1) blocker, and BCS class-III agent. SR tablet formulations of losartan potassium were
formulated using variable quantities of hydroxymethyl propyl cellulose (HPMC) K100M and xanthan gum in combinations
by direct compression technique. The amount of polymers, HPMC K100M, and xanthan gum required to achieve the drug
release was selected as independent variables, X1
and X2
, respectively, whereas time required to release 10% (t10%), 50%
(t50%), 75% (t75%), and 90% (t90%) of drug from formulation was selected as dependent variables. Nine formulations were
prepared and evaluated for various pharmacopoeial tests. Results: The results reveal that all formulations were found to be
with in the pharmacopoeial limits and in vitro drug release profiles of all formulations were subjected to kinetic modeling.
The statistical parameters such as intercept, slope, and correlation coefficient were determined. Polynomial equations were
developed for dependent variables. Validity of developed polynomial equations was checked by designing two checkpoint
formulations (C1
and C2
). According to SUPAC guidelines, formulation (F4
) containing mixture of 15% HPMC K100M
and 20% xanthan gum is the most identical formulation (similarity factor f2 = 86.747, dissimilarity factor f1 = 1.760, and no
significant difference, t = 0.0477) to marketed product (LOSACAR). Conclusion: Best Formulation F4 follows the first-order,
Higuchi kinetics, and the mechanism of drug release was found to be non-Fickian diffusion anomalous transport (n = 0.825).
KEY WORDS: 32 factorial design, First-order kinetics, Hydroxymethyl propyl cellulose K100M, Losartan potassium,
Non-fickian diffusion mechanism, Sustained release tablet, Xanthan gum
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Design, formulation, and in vitro evaluation of sustained release tablets for losartan potassium
1. 315Drug Invention Today | Vol 10 • Issue 3 • 2018
Design, formulation, and in vitro evaluation of sustained
release tablets for losartan potassium
Raghavendra Kumar Gunda, A. Vijayalakshmi*
INTRODUCTION
Oral administration is the most convenient, widely used
route of administration for both prompt drug delivery
systems and new drug delivery systems. Tablets are
the most famous oral solid formulations available in
the market and are preferred by patients and physicians
alike. In case of treatment of chronic disease conditions,
immediate release formulations are required to be
administered in frequent manner and therefore have
patient non-compliance.[1]
However, ingestion of
majority of drugs shows first pass effect and/or first-
pass hepatic metabolism pre-systemic elimination by
gastrointestinal degradation as a result of which low
systemic bioavailability and shorter duration of action
and development of non-active or toxic metabolites.[2]
Research Article
Department of Pharmacognosy, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced
Studies, Pallavaram, Chennai, Tamil Nadu, India
*Corresponding author: A. Vijayalakshmi, Department of Pharmacognosy, School of Pharmaceutical Sciences, Vels Institute
of Science, Technology and Advanced Studies, Pallavaram, Chennai - 600 117, Tamil Nadu, India. Phone: +91-9176093990.
E-mail: avijibaskaran@gmail.com
Received on: 22-10-2017; Revised on: 25-11-2017; Accepted on: 17-02-2018
Access this article online
Website: jprsolutions.info ISSN: 0975-7619
Sustained release (SR) tablet formulations are preferred
for such chronic therapy because they produce patient
compliance, maintain steady-state drug levels, and
dose reduction and increase the safety margin/threshold
for high-potency drugs.[3]
The objective of a SR
formulation is to maintain plasma or tissue drug levels
for prolonged period. SR systems generally do not
attain constant rate of release mechanism and usually
try to mimic zero-order release by providing drug in a
slow first-order manner (i.e., concentration dependent).
Systems that are designated as prolonged release/timed
release will be taken into consideration as attempts at
achieving prolonged and targeted release delivery.[4,5]
SR products provide an advantage over immediate
release formulations by optimizing biopharmaceutical,
pharmacokinetic, and pharmacodynamic properties of
active ingredient. SR formulations have been proved
to improve therapeutic efficacy bythe maintenance of a
steady-state serum drug concentration.[6]
ABSTRACT
Objective: The purpose of the present research investigation was to formulate sustained release (SR) formulations for
losartan potassium using 32
factorial designs. Methods: Losartan potassium is an antihypertensive agent, non-peptide
angiotensin-II receptor (type AT1) blocker, and BCS class-III agent. SR tablet formulations of losartan potassium were
formulated using variable quantities of hydroxymethyl propyl cellulose (HPMC) K100M and xanthan gum in combinations
by direct compression technique. The amount of polymers, HPMC K100M, and xanthan gum required to achieve the drug
release was selected as independent variables, X1
and X2
, respectively, whereas time required to release 10% (t10%
), 50%
(t50%
), 75% (t75%
), and 90% (t90%
) of drug from formulation was selected as dependent variables. Nine formulations were
prepared and evaluated for various pharmacopoeial tests. Results: The results reveal that all formulations were found to be
with in the pharmacopoeial limits and in vitro drug release profiles of all formulations were subjected to kinetic modeling.
The statistical parameters such as intercept, slope, and correlation coefficient were determined. Polynomial equations were
developed for dependent variables. Validity of developed polynomial equations was checked by designing two checkpoint
formulations (C1
and C2
). According to SUPAC guidelines, formulation (F4
) containing mixture of 15% HPMC K100M
and 20% xanthan gum is the most identical formulation (similarity factor f2
= 86.747, dissimilarity factor f1
= 1.760, and no
significant difference, t = 0.0477) to marketed product (LOSACAR). Conclusion: Best Formulation F4
follows the first-order,
Higuchi kinetics, and the mechanism of drug release was found to be non-Fickian diffusion anomalous transport (n = 0.825).
KEY WORDS: 32
factorial design, First-order kinetics, Hydroxymethyl propyl cellulose K100M, Losartan potassium,
Non-fickian diffusion mechanism, Sustained release tablet, Xanthan gum
2. Raghavendra Kumar Gunda and A. Vijayalakshmi
Drug Invention Today | Vol 10 • Issue 3 • 2018316
The utilization of polymers in controlling the drug
release rate has become an important tool in the
product development of pharmaceutical dosage
forms. Over many years, various studies have been
reported in the literature on the applicability of
polymers in the formulation development of sustained
drug release systems for various drugs. Natural
polymers preferred primarily because they were
economic, high drug holding capacity, high thermal
stability, non-carcinogenicity, mucoadhesivity,
biodegradable, biocompatible, broad regulatory
acceptance, and ease of compression. Various gums
and mucilages were used for the development of SR
formulations in the past few decades such as xanthan
gum, alginates, guar gum, tragacanth gum, pectin,
and cellulose derivatives such as hydroxypropyl
cellulose, hydroxymethyl propyl cellulose (HPMC),
carboxymethyl cellulose (CMC), and sodium CMC
have been extensively studied as release retardants
in the prolonged release formulations. The future of
SR products is promising in novel drug delivery area
such as chronopharmacotherapeutic delivery system,
mucoadhesive system, chronopharmacokinetic
system, targeted drug delivery system, and particulate
system that provide high promise and acceptability.
Oral SR formulations by direct compression technique
were a simple approach due to its ease, faster
production. No hydrolytic or oxidative reactions were
occurred during manufacturing and compliance.[7]
The suitability of drug candidates for SR system was
based on biopharmaceutical, pharmacokinetic, and
pharmacodynamic properties of it.
MATERIALS AND METHODS
Materials
Materials used in this study were obtained from the
different sources. Losartan potassium was a gift sample
from Aurobindo Pharma Ltd., Hyderabad, India.
HPMC K100M, xanthan gum, MCC, and lactose were
procured from Loba Chemie Pvt. Ltd., Mumbai. Other
excipients such as magnesium stearate and Talc were
procured from S.D. Fine Chem. Ltd., Mumbai.
Drug profile and rationality for experimental
design
In the present research investigation, a SR formulation
of losartan potassium has been developed that reduces
dosing frequency. Losartan potassium was a non-
peptide angiotensin-II receptor (type AT1
) blocker,
used for the management of hypertension. The main
problem associated with this drug is its low therapeutic
effectiveness due to poor bioavailability (25–35%)
and shorter biological half-life (2 ± 0.5 h). Prompt
release tablets should be administered 2–3 times a
day to maintain steady-state level. Administration
of losartan potassium in a SR formulation would be
more beneficial for the management of hypertension.
Hence, to improve therapeutic efficacy, reduce dosing
frequency, and for better patient compliance, once
daily SR losartan potassium is desirable.[8-15]
The study was carried out to design, formulate, and
evaluate SR tablet formulation of losartan potassium
as a model drug and had an aim that final batch
formulation parameters should meetthe objective
ofthe present study.
Itisanimportantissue,fordesigningabestformulation
with an desired and predicted release rate in a shorter
time period and less heuristics. Response surface
methodology (RSM) utilizing a polynomial equation
has been prominently used. Various types of RSM
designs include Box–Behnken design, 32
factorial
design, central composite design, and D-optimal
design. RSM is applicable when only a few significant
factors are involved in experimental optimization. The
technique needs less experimentation and time, thus
proving to be far more effective and cost-effective
than the traditional methods of formulation designs.[3-6]
Hence, an trail is made in this research investigation to
formulate SR tablet formulations of losartan potassium
using HPMC K100M and xanthan gum. Instead of
heuristic method, a standard statistical optimization
methodisemployedtoevaluatetheeffectofformulation
variables on the release properties. Large-scale
production requires more simplicity in the formulation
with the economic point of view in all aspects.
A 32
full factorial design was utilized to study the
drug release profile in a systematic approach. A 32
full
factorial design was employed to examine the effect of
two independent variables (factors), i.e. the quantities
of HPMC K100M and xanthan gum on the dependent
variables, i.e., t10%
, t50%
, t75%
, and t90%
(time required
to release 10%, 50%, 75%, and 90% of drug from
formulation, respectively).
Formulation development of losartan potassium
SR tablets
The factorial design is a statistical optimization
technique that allows identification of factors involved
in a method and assesses their relative importance. In
addition, any interaction between factors chosen can
be identified. The development of a factorial design
involves the selection of variables (factors) and the
choice of responses.[3-6]
32
factorialdesign describes the proportion in which
the independent variables, i.e., quantities of HPMC
K100M and xanthan gum were used inthe formulation
of losartan potassium SR tablets. The time required
to release 10% (t10%
), 50% (t50%
), 75% (t75%
), and 90%
(t90%
) drug from formulation was selected as dependent
variables. Significance terms were chosen at 95%
3. Raghavendra Kumar Gunda and A. Vijayalakshmi
317Drug Invention Today | Vol 10 • Issue 3 • 2018
confidence interval (P < 0.05) for final resultant
equations. Polynomial equations were developed for
t10%
, t50%
, t75%
, and t90%
,using step-wise backward linear
regression analysis.
The three levels of factor X1
(HPMC K100M) at a
concentration of 10%, 15%, and 20% and three levels
of factor X2
(xanthan gum) at a concentration of 10%,
15%, and 20% (% with respect to total tablet weight)
were taken as the rationale for the design of the
losartan potassium SR tablet formulation. A total of
nine losartan potassium SR tablet formulations were
prepared employing selected combinations of the two
factors, i.e., X1
and X2
as per 32
factorial design and
evaluated to find out the significance of combined
effects of X1
and X2
to select the best combination
and the concentration required to achieve the desired
prolonged/SR of drug from the dosage form.
Preparation of losartan potassium SR tablets
Losartan potassium SR tablets were processed by
direct compression technique. Formulae of each tablet
are shown in Table 1. All ingredients required for
formulation were collected and weighed accurately
and passed through sieve no 40. They were mixed
uniformly in a polybag or triturate for 15 min. Add
magnesium stearate and then again blend for 5–6 min.
Blend was subjected to compression using 8 station
rotary tablet punching machine (Minipress, RIMEK,
Ahmedabad) using 8 mm circular punches and the
same hardness used for required number of tablets.
Tablets were evaluated as per pharmacopoeial and
unofficial tests. Tablets were packaged in airtight,
light resistance containers.
Experimental design
Experimental design employed in the present research
work for the optimization of retardants concentration
such as quantity of HPMC K100M was taken as
X1
and quantity of xanthan gum was taken as X2
.
Experimental design is presented in Table 2. Three
levels for X1
were selected and coded as −1 = 10%,
0 = 15%, and +1 = 20%. Three levels for the X2
were
selected and coded as −1 = 10%, 0 = 15%, and +1
= 20%. Formulae for all the experimental trails are
presented in Table 1.
Evaluation of losartan potassium SR tablets
Hardness
The hardness of the tablets was determined by
diametric breakdown of tablet using a Monsanto
hardness tester. A tablet hardness of about 2–4 kg/cm2
is considered adequate for breaking strength.[16]
Friability
The friability of the tablets was executed using Roche
friabilator. A sample of 20 tablets are taken, weighed
(W), and dedusted in a drum for 4 min at a speed of
25 rpm or 100 free falls and weighed (W1
) again.
Percentage friability was calculated from the loss in
weight as given in equation as below. The weight loss
should not be more than 0.8%.
Friability (%) = [(W−W1
)/W)] × 100
Content uniformity
In this test, 20 tablets were randomly selected and
assay was performed, and the tablets having not
<85% or more than 115% of the labeled claim can be
considered as passes the test.
Assay
The drug content in each formulation was determined
by triturating 20 tablets and powder equivalent to
40 mg was dissolved in 100 ml of phosphate buffer
pH 6.8, followed by agitation. The solution was
filtered through a 0.45 μ membrane filter and diluted
suitably, and the absorbance of resultant solution was
measured spectrophotometrically at 254 nm using
phosphate buffer pH 6.8 as blank.
Thickness
Thickness of the all tablet formulations was measured
using Vernier calipers by placing tablet between two
arms of the Vernier calipers.
In vitro dissolution study
The in vitro dissolution study for the losartan
potassium SR tablets was carried out in USP XXIII
type-II dissolution test apparatus (Paddle type) using
900 ml of 0.1 N HCl as dissolution medium for first
2 h followed by phosphate buffer pH 6.8 at 50 rpm
Table 1: Formulae for the preparation of losartan potassium sustained release tablets
Name of ingredients Quantity of ingredients per each tablet (mg)
F1
F2
F3
F4
F5
F6
F7
F8
F9
Losartan potassium 50 50 50 50 50 50 50 50 50
Emcompress 46 56 66 56 66 76 66 76 86
Microcrystalline cellulose pH‑103 20 20 20 20 20 20 20 20 20
HPMC K100M 40 40 40 30 30 30 20 20 20
Xanthan gum 40 30 20 40 30 20 40 30 20
Magnesium stearate 2 2 2 2 2 2 2 2 2
Talc 2 2 2 2 2 2 2 2 2
Total weight 200 200 200 200 200 200 200 200 200
HPMC: Hydroxymethyl propyl cellulose
4. Raghavendra Kumar Gunda and A. Vijayalakshmi
Drug Invention Today | Vol 10 • Issue 3 • 2018318
and temperature 37 ± 0.5°C. 5 ml of the samples
were withdrawn by means of a syringe fitted with a
pre-filter at predetermined time intervals, and the
volume withdrawn at each interval was replaced with
the same quantity of fresh dissolution medium. The
resultant samples were analyzed for the presence
of the drug release by measuring the absorbance at
254 nm using UV visible spectrophotometer after
suitable dilutions. The determinations were performed
in triplicate (n = 3).
Kinetic modeling of drug release
The dissolution profile of all the formulations was
fitted in to zero-order, first-order, Higuchi and
Korsmeyer–Peppas models to ascertain the kinetic
modeling of drug release.[17,18]
RESULTS AND DISCUSSION
SR tablets of losartan potassium were prepared and
optimized by 32
factorial designs to select the best
combination quantities of drug release retardants,
HPMC K100M, and xanthan gum and also to achieve
the desired prolonged release of drug from the
formulation. The 2 factorial parameters involved in the
development of formulations are amounts of HPMC
K100M and xanthan gum as independent variables
(X1
and X2
) and in vitro drug release parameters such
Figure 1: Comparative zero-order plots for F1
–F9
Figure 2: Comparative first-order plots for F1
–F9
Figure 3: Comparative Higuchi plots for F1
–F9
Figure 4: Comparative Korsmeyer–Peppas plots for F1
–F9
as t10%
, t50%
, t75%
, and t90%
as dependent variables. Nine
formulations were prepared using 3 levels of 2 factors,
and all the formulations containing 50 mg of losartan
potassium were prepared as a SR tablet formulation
by direct compression method as per the formulae
presented in Table 1.
All the tablets were subjected to different
pharmacopoeial tests such as drug content, mean
hardness, friability, and mean thickness as per official
methods. The crushing strength of tablets was found
to be in the range of 4.525 ± 0.43–5.07 ± 0.42 kg/cm2
.
Weight loss in the friability test was <0.445%. Drug
content of prepared tablets was within acceptance
range only. Results for all quality control tests were
summarized in Table 3.
In vitro drug release rate studies were performed for
prepared tablets using 0.1 N HCl for first 2 h followed
by phosphate buffer pH 6.8 as a dissolution medium
and operated at 50 rpm speed and temperature
37 ± 0.5°C using USP XXIII type-II dissolution test
apparatus. Comparative kinetic plots for all prepared
formulations are shown in Figures 1-4, and the
dissolution parameters are summarized in Table 4.
The percentage of drug release for formulations F1
–F9
at 12 h was found to be in the range of 89.20–96.325%.
5. Raghavendra Kumar Gunda and A. Vijayalakshmi
319Drug Invention Today | Vol 10 • Issue 3 • 2018
From the result, it reveals that the release rate was
higher for formulations containing a low level of
HPMCK100M compared with other formulations
containing higher level, and due to high concentration
of retardant the drug may have entrapped within a
polymer matrix causing a decrease in the rate of drug
release. Therefore, desired rate of drug release can be
obtained by manipulating the quantities of retardants.
Much difference was observed in the dependent
variables due to formulation variables. Formulation
F4
containing 30 mg of HPMC K100M and 40 mg of
xanthan gum showed promising results (t10%
=
0.383 h,
t50%
= 2.519 h, t75%
= 5.038 h, and t90%
= 8.371 h).
The variation in initial burst result is a result of the
difference in the thickness of polymeric matrix.
The increase in viscosity results in a corresponding
decrease in the drug release, which might be due to
the result of thicker gel layer formulation.
The in vitro dissolution data of losartan potassium SR
tablet formulations were subjected to various kinetic
modeling by goodness of fit by linear regression
analysis. The results of kinetic modeling are shown
in Table 4. The results also reveal that majority of
formulations follows first-order kinetics and r values
were found to be above 0.974 (0.974–0.982). The
Figure 5: Response surface plots for t10%
Figure 6: Response surface plots for t50%
r values for Higuchi equation were found to be in
the range of 0.956–0.965, which shows that the drug
release follows diffusion mechanism. Kinetic data were
fitted to Peppas equation, the slope (n) values range
from 0.67 to 0.902 that shows non-Fickian diffusion
mechanism (anomalous drug transport). Polynomial
equations were derived for all dependent variables
using backward stepwise linear regression analysis
using PCP Disso software, and response surface plots
were constructed using SIGMAPLOT V13 software.
The response surface plots are shown in Figures 5-8
for t10%
, t50%
, t75%
, and t90%
using X1
and X2
on both the
Table 2: Experimental design layout
Formulation code X1
X2
F1
1 1
F2
1 0
F3
1 −1
F4
0 1
F5
0 0
F6
0 −1
F7
−1 1
F8
−1 0
F9 −1 −1
C1
−0.5 −0.5
C2
+0.5 +0.5
Figure 7: Response surface plots for t75%
Figure 8: Response surface plots for t90%
6. Raghavendra Kumar Gunda and A. Vijayalakshmi
Drug Invention Today | Vol 10 • Issue 3 • 2018320
axes, respectively. The kinetic parameters for factorial
formulations F1
to F9
are presented in Table 5.
Polynomial equation for 3² full factorial designs was
explained as follows:
Y=b0
+b1
X1
+b2
X2
+b12
X1
X2
+b11
X1
²+b22
X2
²
Where Y is dependent variable, b0
is average response
of 9 trails, and b1
is estimated coefficient for X1
. The
main effects (X1
and X2
) represent the average result
of changing one factor at a time from its low to high
value. The interaction term (X1
X2
) shows how the
response changes when two factors are simultaneously
changed. The polynomial terms (X1
² and X2
²) are
included to investigate non-linearity. The validity
of derived equations was verified by designing two
checkpoint formulations of intermediate concentration
(C1
and C2
).
The polynomial equations for dependent variables
developed are as follows:
Y1
=0.378+0.054X1
+0.0218X2
-0.004X1
X2
+0.0406
X1
2
+0.0252X2
2
(for t10%
)
Y2
=2.488+0.358X1
+0.1434X2
-0.025 X1
X2
+0.2687
X1
2
+0.167 X2
2
(for t50%
)
Y3
=4.976+0.717X1
+0.287X2
-0.049 X1
X2
+0.537 X1
2
-
0.334 X2
2
(for t75%
)
Y4
=8.268+1.191X1
+0.476X2
-0.081 X1
X2
+0.892
X1
2
+0.554 X2
2
(for t90%
)
The positive sign for coefficient of X1
in Y1
, Y2
,
Y3
, and Y4
equations indicates that, as the quantity
of HPMC K100M increases, t10%
, t50%
, t75%
, and t90%
value increases. In other words, the data explain
that both X1
and X2
affect the responses. From the
results, it can be concluded that an increase in the
quantity of the retardants leads to decrease in the
rate of drug release and drug release pattern may be
changed by appropriate selection of the X1
and X2
levels. The dissolution parameters for predicted from
the polynomial equations derived and those actual
observed from experimental results are presented in
Table 6.
The closeness of predicted and observed values for
dependent variables indicates the validity of derived
equations.Theresponsesurfaceplotswerepresentedto
Table 3: Post‑compression parameters
Formulation
code
Hardness (kg/cm2
) Thickness (mm) Friability (%) % Weight
variation
Drug
content (%)
F1
4.525±0.43 3.29±0.13 0.260±0.07 199.47±1.4 97.88±1.2
F2
4.73±0.40 3.32±0.13 0.357±0.025 199.88±1.32 99.05±1.5
F3
4.823±0.41 3.44±0.12 0.398±0.46 201.76±1.31 99.97±1.6
F4
5.07±0.42 3.52±0.15 0.44±0.007 202.23±1.45 99.93±1.5
F5
4.97±0.4 3.57±0.14 0.362±0.02 201.98±1.5 99.89±1.4
F6
4.96±0.398 3.55±0.12 0.44±0.005 203.8±1.5 101.18±1.5
F7
5.07±0.41 3.53±0.05 0.44±0.04 201.39±1.42 100.02±1.45
F8
4.96±0.39 3.58±0.12 0.363±0.06 202.86±1.4 100.9±1.36
F9
4.96±0.4 3.54±0.11 0.444±0.02 203.8±1.2 101.18±1.44
Table 4: Statistical parameters
Formulation
code
Kinetic parameters
Zero order First order Higuchi Korsmeyer–Peppas
a b r a b r a b r a b r
F1
1.064 9.166 0.973 2.099 0.097 0.979 23.237 33.837 0.956 0.670 1.346 0.992
F2
0.309 9.339 0.972 2.108 0.107 0.982 22.744 34.710 0.961 0.719 1.317 0.990
F3
0.525 9.290 0.971 2.101 0.104 0.982 22.506 34.575 0.961 0.713 1.326 0.989
F4
0.466 9.554 0.971 2.129 0.119 0.975 22.954 35.426 0.958 0.825 1.196 0.992
F5
1.736 9.714 0.970 2.156 0.137 0.975 22.476 36.220 0.962 0.872 1.164 0.991
F6
1.896 9.707 0.970 2.153 0.136 0.974 22.338 36.213 0.962 0.887 1.145 0.991
F7
1.822 9.574 0.968 2.125 0.124 0.976 22.183 35.770 0.962 0.845 1.190 0.988
F8
3.092 9.735 0.965 2.154 0.143 0.976 21.705 36.564 0.965 0.888 1.160 0.986
F9
3.252 9.727 0.965 2.152 0.142 0.975 21.567 36.557 0.965 0.902 1.143 0.986
F1
to F9
are factorial formulations, r: Correlation coefficient, a: Intercept, b: Slope
Table 5: Dissolution parameters of losartan potassium
SR tablets
Formulation
code
Kinetic parameters
t50% (h)
t10% (h)
t90% (h)
t75% (h)
F1
3.107 0.472 10.324 6.214
F2
2.818 0.428 9.364 5.636
F3
2.883 0.438 9.580 5.766
F4
2.519 0.383 8.371 5.038
F5
2.203 0.335 7.320 4.406
F6
2.205 0.335 7.328 4.410
F7
2.435 0.370 8.091 4.870
F8
2.110 0.321 7.011 4.220
F9
2.113 0.321 7.022 4.226
7. Raghavendra Kumar Gunda and A. Vijayalakshmi
321Drug Invention Today | Vol 10 • Issue 3 • 2018
show the effects of independent variables on dependent
variables. The final best (optimized) formulation (F4
)
when compared with marketed product (LOSACAR)
shows similarity factor (f2
) 86.74689, difference factor
(f1
) 1.759915 (there is no significant difference in drug
release because tcal
is <0.05).
CONCLUSION
The present research theme envisions the use of release
retardants such as HPMC K100M and Xanthan gum in
the formulation development of SR tablets of losartan
potassium with the help of 32
factorial statistical
design technique. From the results, it reveals that the
amount of retardant (HPMC) is inversely proportional
to the rate of drug release. Combination of retardants
used since there is no incompatibility with the drug
which may be more favorable for obtaining desired
prolonged release of the drug. The best formulation
(F4
) follows Higuchi kinetics while the drug release
mechanism was found to be non-Fickian diffusion
(anomalous transport), first-order release type. On
the basis of evaluation parameters, the optimized
formulation F4
may be used the management of
hypertension and to reduce the risk of stroke, heart
attack, and cardiovascular disease. This may improve
the patient compliance by reducing the dosing
frequency. We could be able to minimize the per oral
cost of the formulation.
ACKNOWLEDGMENT
Authors acknowledge sincere thanks to the
management for the facilities granted for the research
work.
REFERENCES
1. Jain S, Mehra NK, Singhai AK, Saraogi GK. Development and
evaluation of sustained release matrix tablet of lamivudine.
Int J Pharm Sci Res 2011;2:454-61.
2. Singh RR. Design, formulation and in vitro evaluation of
lamivudine Hcl sustained release tablets. Int J Res Pharm Nano
Sci 2014;3:113-21.
3. Gunda RK, Kumar JN, Babu CA, Anjaneyulu MV. Formulation
development and evaluation of lamotrigine sustained
release tablets using 32
factorial design. Int J Pharm Sci Res
2015;6:1746-52.
4. Bankar GS, Rhodes CT, editors. Modern Pharmaceutics. 3rd
ed.
New York: Marcel Dekker, Inc.; 1996. p. 668-9.
5. Lachmann L, Lieberman HA, Kanig JL. The Theory and
Practice of Industrial Pharmacy. 3rd
ed. Bombay: Varghese
Publishing House; 1991. p. 430.
6. Gunda RK. Formulation development and evaluation of
rosiglitazone maleate Sustained release tablets using 32
factorial
design. Int J Pharm Tech Res 2015;8:713-24.
7. Bankar GS, Rhodes CT, editors. Modern Pharmaceutics.
4th
ed. USA: Marcel Dekker, Inc.; 2003. p. 503-5.
8. Krishna KM, Arunkumar S. Formulation and evaluation of
losartan potassium sustained release matrix tablets. Res J
Pharm Biol Chem Sci 2012;3:524-33.
9. Uddin M, Halder S, Kumar U, Rouf AS. Design and evaluation
of once daily losartan potassium sustained release matrix tablet.
Int J Pharm Sci Res 2014;5:519-25.
10. Mohanty S, Dev A, Tripathy S. Formulation and evaluation of
losartan potassium sustained release tablets. Int J Pharm Pharm
Sci 2012;4:390-2.
11. Suryadevara V, Lankapalli SR, Vejella UM, Mupparaju S,
Chava S. Formulation and evaluation of losartan potassium
osmotic controlled matrix tablets. Indian J Pharm Educ
2014;48S:18-26.
12. Shanmugam S, Chakrahari R, Sundaramoorthy K. Formulation
and evaluation of sustained release matrix tablets of losartan
potassium. Int J Pharm Tech Res 2011;3:526-34.
13. Sasidhar RL, Vidyadhara S, Babu JR, Nagaraju R, Reddy KP.
Formulation and evaluation of controlled release of losartan
potassium matrix tablets using poly (Ethyleneoxides). Curr
Trends Biotechnol Pharm 2009;3:440-6.
14. Gollapudi R, Javvaji H, Tadikonda RR. Formulation and
in vitro evaluation of sustained release matrix tablets of losartan
potassium. Pharmanest 2011;2:31-6.
15. Sarwar MS, Hossain MS. Development and evaluation
of sustained release losartan potassium matrix tablet
using Kollidon SR as release retardant. Braz J Pharm Sci
2012;48:621- 8.
16. Kharia AA, Hiremath SN, Singhai AK, Omray K, Jain SK.
Design and optimization of floating drug delivery system of
acyclovir. Indian J Pharm Sci 2010;72:599-606.
17. Higuchi T. Mechanism of sustained-action medication.
Theoretical analysis of rate of release of solid drugs dispersed
in solid matrices. J Pharm Sci 1963;51:1145-9.
18. Peppas NA. Analysis of fickian and non-fickian drug release
from polymers. Pharm Acta Helv 1985;60:110-1.
19. Dortunc B, Gunal N. Release of acetazolamide from swellable
HPMC matrix tablets. Drug Dev Ind Pharm 1997;23:1245-9.
Table 6: Dissolution parameters for predicted and observed values for checkpoint formulations
Formulation
code
Predicted value Actual observed value
t10% (h)
t50% (h)
t75% (h))
t90% (h)
t10% (h)
t50% (h)
t75% (h))
t90% (h)
C1
0.356 2.334 4.680 7.776 0.357 2.338 4.685 7.775
C2
0.431 2.841 5.684 9.443 0.433 2.845 5.681 9.448
Source of support: Nil; Conflict of interest: None Declared