Objective: The purpose of present research work is to develop the sustained release formulation for Telmisartan using 32 factorial design. Telmisartan an Antihypertensive agent, nonpeptide angiotensin-II receptor (type AT1) antagonist and BCS class-II agent. Methods: Sustained Release tablet formulations of Telmisartan were prepared using different quantities of HPMCK100M and Xanthan Gum in combinations by direct compression technique. The concentration of Polymers, HPMCK100M and Xanthan gum required to achieve the drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Nine formulations were prepared and are evaluated for various pharmacopoeial tests. Results: The results reveals that all formulations were found to be with in the pharmacopoeial limits and In vitro drug release profiles of all formulations were fitted in to various Kinetic models. The statistical parameters like intercept, slope & correlation coefficient were calculated. Polynomial equations were developed for dependent variables. Validity of developed polynomial equations were checked by designing 2 check point formulations (C1, C2). Conclusion: According to SUPAC guidelines formulation (F5) containing combination of 15% HPMCK100M and 15% Xanthan gum, is the most identical formulation (similarity factor f2= 90.863, dissimilarity factor f1= 1.665 & No significant difference, t= 0.03379) to marketed product (TELVAS). Best Formulation F5 follows First order, Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion Anomalous Transport. (n= 0.828).

1. Vol 7 Suppl 3, July- Sep 2018 www.mintagejournals.com 22
Research Article
DESIGN, FORMULATION AND IN VITRO EVALUATION OF TELMISARTAN SUSTAINED
RELEASE TABLETS
RAGHAVENDRA KUMAR GUNDA*1
, PRASADA RAO MANCHINENI2
1
Assistant Professor, Department of Pharmaceutics, M.A.M college of Pharmacy, Kesanupalli (V), Narasaraopet, Guntur (Dt), Andhra
Pradesh, India-522601,Professor cum Principal,Department of Pharmaceutical Analysis, M.A.M college of Pharmacy, Kesanupalli (V),
Narasaraopet, Guntur (Dt), Andhra Pradesh, India-522601.Email:raghav.gunda@gmail.com
Received - 10.07.2018; Reviewed and accepted - 31.07.2018
ABSTRACT
Objective: The purpose of present research work is to develop the sustained release formulation for Telmisartan using 32 factorial design. Telmisartan an
Antihypertensive agent, nonpeptide angiotensin-II receptor (type AT1) antagonist and BCS class-II agent. Methods: Sustained Release tablet formulations
of Telmisartan were prepared using different quantities of HPMCK100M and Xanthan Gum in combinations by direct compression technique. The
concentration of Polymers, HPMCK100M and Xanthan gum required to achieve the drug release was selected as independent variables, X1 and X2
respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Nine
formulations were prepared and are evaluated for various pharmacopoeial tests. Results: The results reveals that all formulations were found to be with in
the pharmacopoeial limits and In vitro drug release profiles of all formulations were fitted in to various Kinetic models. The statistical parameters like
intercept, slope & correlation coefficient were calculated. Polynomial equations were developed for dependent variables. Validity of developed polynomial
equations were checked by designing 2 check point formulations (C1, C2). Conclusion: According to SUPAC guidelines formulation (F5) containing
combination of 15% HPMCK100M and 15% Xanthan gum, is the most identical formulation (similarity factor f2= 90.863, dissimilarity factor f1= 1.665 & No
significant difference, t= 0.03379) to marketed product (TELVAS). Best Formulation F5 follows First order, Higuchi’s kinetics, and the mechanism of drug
release was found to be Non-Fickian Diffusion Anomalous Transport. (n= 0.828).
Keywords :Telmisartan, 32 Factorial Design, Sustained Release, HPMCK100M , Xanthan gum, First order kinetics.
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, conventional formulations are required to be
administered in frequent manner and therefore have several
disadvantages [1]. However, ingestion of many drugs are
subjected to extensive presystemic elimination by gastrointestinal
degradation and/or first pass hepatic metabolism as a result of
which low systemic bioavailability and shorter duration of action
and formation of non-active or toxic metabolites.
Sustained release (SR) tablet formulations are preferred for such
chronic therapy because they produce patient compliance,
maintain steady state drug levels, dose reduction, and increases
the margin of safety for high-potency drugs. The objective of a
sustained release dosage form is to maintain plasma or tissue
drug levels for prolonged period. This is usually achieved by
attempting to get zero-order release from the dosage form. Zero-
order release constitutes the drug release rate from the dosage
form that is independent of the amount of drug in the delivery
system (i. e., constant release rate). Sustained release systems
generally do not attain this type 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 can also be
considered as attempts at achieving prolonged release delivery
[2].
Sustained release formulations allowing greater reduction in
dosing frequency in comparison with the frequency required by a
conventional release dosage form [3]. Sustained release products
provide advantage over immediate release dosage form by
optimising biopharmaceutical, pharmacokinetic and
pharmacodynamic properties of drug. Sustained release
formulations have been demonstrated to improve therapeutic
efficacy by maintenance of a steady state serum drug
concentration.
The utilization of polymers in controlling the drug release has
become an important tool in the formulation development of
pharmaceutical dosage forms. Over many years, numerous
studies have been reported in the literature on the application of
hydrophilic polymers in the development of Sustained drug
release systems for various drugs [3].
Natural polymers preferred primarily because they were
economic, readily available, be capable of chemical modifications,
mucoadhesivity, non-toxic, non-carcinogenicity, high thermal
stability, biodegradable, biocompatible, high drug holding capacity
and broad regulatory acceptance, molecular size, diffusivity, pKa-
ionization constant, release rate, dose and stability, duration of
action, absorption window, therapeutic index, protein binding and
ease of compression[4]. This led to its application as Formulation
aid in hydrophilic drug delivery system. The numerous natural
gums and mucilages have been examined as polymers for
sustained drug release in the last few decades for example; guar
gum, tragacanth gum, xanthan gum, pectin, alginates etc. In the
development of a sustained release tablet dosage form. Cellulose
derivatives such as CMC, HPMC, HPC, SCMC, have been
extensively used as polymer in the sustained release
formulations.
Oral sustained release formulations by direct compression
technique was a simple approach of drug delivery systems that
proved to be rational in the pharmaceutical arena for its ease,
compliance, faster production, avoid hydrolytic or oxidative
reactions occurred during processing of dosage forms. The
selection of the drug candidates for sustained release system
needs consideration of several biopharmaceutical,
pharmacokinetic and pharmacodynamic properties of drug
molecule [5].
Drug Profile and Rationality for Experimental Design:
In the present study, a sustained release dosage form of
Telmisartan has been developed that makes less frequent
administering of drug.
Vol 7, Suppl 3, 2018 ISSN: 2320-3315
Mintage Journal of Pharmaceutical & Medical Sciences

2. Gunda et al Mintage journal of Pharmaceutical & Medical Sciences│22-27
Vol7 Suppl 3, July- Sep 2018 www.mintagejournals.com 23
Telmisartan was a nonpeptide angiotensin-II receptor (type AT1)
antagonist. It blocks the vasoconstrictor and aldosterone-
secreting effects of angiotensin-II by selectively blocking its
binding to the AT1 receptor in adrenal gland and smooth muscles
of vasculature. Following oral administration, peak concentrations
(Cmax) of telmisartan are achieved in the 1st
hour. The
bioavailability of orally administered telmisartan is nonlinear [6]. It
was practically insoluble in water and other aqueous media. The
very poor aqueous solubility and wettability of Telmisartan give
rise to difficulties in the design of pharmaceutical formulations and
led to variable oral bioavailability. Thus, there is a need to improve
rate of drug release. Hence, the study was carried out to design,
formulate and evaluate sustained release tablet formulation of
Telmisartan as a model drug and had an aim that final batch
formulation parameters should meet objective of present work.
It is an important issue is to design an best formulation with an
appropriate release rate in a short time period and minimum
heuristics. response surface methodology (RSM) utilizing a
polynomial equation has been prominently used. Different types of
RSM designs include 3-level factorial design, central composite
design (CCD), Box-Behnken design and D-optimal design.
Response surface methodology (RSM) is used when only a few
significant factors are involved in experimental optimization. The
technique requires less experimentation and time, thus proving to
be far more effective and cost-effective than the traditional
methods of formulating sustained release dosage forms [7].
Hence an attempt is made in this research work to formulate SR
formulations of Telmisartan using HPMCK100M and Xanthan
gum. Instead of heuristic method, a standard statistical tool design
of experiments is employed to study the effect of formulation
variables on the release properties.
Large scale production needs more simplicity in the formulation
with economic and cheapest dosage form.
A 32
full factorial design was employed 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 amounts of HPMCK100M and Xanthan gum on
the dependent variables, i.e. t10%, t50%, t75%, t90%,(Time taken to
release 10%,50%,75%,90% respectively).
MATERIALS AND METHODS
Materials used in this study were obtained from the different
sources. Telmisartan was a gift sample from Aurobindopharma
Ltd, Hyderabad, India. HPMCK100M, Xanthan gum, Avicel and
Lactose were procured from Loba Chemie Pvt. Ltd, Mumbai.
Other excipients such as magnesium stearate, Talc were
procured from S.D. Fine Chem. Ltd., Mumbai.
Formulation Development of Telmisartan Sustained Release
Tablets:
The factorial design is a technique that allows identification of
factors involved in a process and assesses their relative
importance. In addition, any interaction between factors chosen
can be identified. Construction of a factorial design involves the
selection of parameters and the choice of responses [8].
A selected three level, two factor experimental design (32
factorial
design) describe the proportion in which the independent
variables quantities of HPMCK100M and Xanthan gum were used
in formulation of Telmisartan sustained release Tablets. The time
required for 10% (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) drug
dissolution were selected as dependent variables. Significance
terms were chosen at 95% confidence interval (p<0.05) for Final
resultant Equations. Polynomial equations were developed for
t10%, t50%, t75%, t90%,(step-wise backward Linear Regression
Analysis).
The three levels of factor X1 (HPMCK100M) at a concentration of
10%, 15%, 20%. three levels of factor X2 (Xanthan gum) at a
concentration of 10%, 15%, 20%.(% with respect to total tablet
weight) was taken as the rationale for the design of the
Telmisartan SR tablet formulation. Totally nine Telmisartan
sustained release tablet formulations were prepared employing
selected combinations of the two factors i.eX1,X2 as per 32
Factorial and evaluated to find out the significance of combined
effects of X1,X2 to select the best combination and the
concentration required to achieve the desired prolonged/
sustained release of drug from the dosage form.
Preparation of Telmisartan Sustained Release Tablets
Telmisartan SR Tablets were prepared by Direct Compression
method. Composition of each Tablet was shown in Table 2. 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 10 minutes. Magnesium
stearate was added and then again blend for 5-6 minutes, Blend
was subjected to compression by using 8 station rotary tablet
punching machine ( Minipress, RIMEK), Ahmedabad) using 8 mm
circular punches and same hardness used for required number of
tablets. Compressed tablets were examined as per official
standards and unofficial tests. Tablets were packaged in well
closed light resistance and moisture proof containers.
Experimental Design
Experimental design utilized in present investigation for the
optimization of polymer concentration such as, concentration of
HPMCK100M was taken as X1 and concentration of Xanthan gum
was taken as X2. Experimental design was given in Table 1. Three
levels for the Concentration of HPMCK100M were selected and
coded as -1= 10%, 0=15%, +1=20%. Three levels for the
Concentration of Xanthan gum were selected and coded as -1=
10%, 0=15%, +1=20%. Formulae for all the experimental batches
were given in Table 2.
Table 1: Experimental Design Layout
Table 2: Formulae for the Preparation of Telmisartan Sustained Release Tablets
Name of Ingredients
Quantity of Ingredients per each Tablet (mg)
F1 F2 F3 F4 F5 F6 F7 F8 F9
Telmisartan 40 40 40 40 40 40 40 40 40
Lactose Mono Hydrate 85 97.5 110 97.5 110 122.5 110 122.5 135
Avicel pH-103 20 20 20 20 20 20 20 20 20
HPMCK100M 50 50 50 37.5 37.5 37.5 25 25 25
Xanthan gum 50 37.5 25 50 37.5 25 50 37.5 25
Magnesium Stearate 3 3 3 3 3 3 3 3 3
Talc 2 2 2 2 2 2 2 2 2
Total Weight 250 250 250 250 250 250 250 250 250
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

3. Vol 7 Suppl 3, July- Sep 2018 www.mintagejournals.com 24
EVALUATION OF TELMISARTAN SUSTAINED RELEASE
TABLETS
Hardness
The hardness of the tablets was tested by diametric breakdown of
tablet using a Monsanto Hardness Tester. A tablet hardness of
about 2-4 kg/cm2
is considered adequate for mechanical stability.
Friability
The friability of the tablets was performed by using Roche
friabilator. Tablets of a known weight (W0) or a sample of 20
tablets are dedusted in a drum for a fixed time i.e 4 minutes at a
speed of 25 rpm and weighed (W) again. Percentage friability was
calculated from the loss in weight as given in equation as below.
The weight loss should not be more than 1 %.
Friability (%) = [(Initial weight- Final weight) / (Initial weight)]
x 100
Content Uniformity
In this test, 20 tablets were randomly selected and the percent
drug content was determined, the tablets contained not less than
85% or more than 115% of the labelled drug content can be
considered as the test was passed.
Assay
The drug content in each formulation was determined by
triturating 20 tablets and powder equivalent to 40 mg was
dissolved in 100ml of phosphate buffer pH 6.8, followed by
stirring. The solution was filtered through a 0.45μ membrane filter,
diluted suitably and the absorbance of resultant solution was
measured spectrophotometrically at 223 nm using phosphate
buffer pH 6.8 as blank.
Thickness
Thickness of the all tablet formulations were 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 Telmisartan sustained
release tablets were 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 two hours followed by phosphate
buffer pH 6.8 at 50 rpm and temperature 37±0.5°C. At
predetermined time intervals, 5 ml of the samples were withdrawn
by means of a syringe fitted with a pre-filter, the volume withdrawn
at each interval was replaced with same quantity of fresh
dissolution medium. The resultant samples were analyzed for the
presence of the drug release by measuring the absorbance at 223
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 [9-10].
RESULTS AND DISCUSSION
Sustained release tablets of Telmisartan were prepared and
optimized by 32
factorial design in order to select the best
combination of different drug release retardants, HPMCK100M,
Xanthan gum and also to achieve the desired sustained release of
drug from the Formulation. The two factorial parameters involved
in the development of formulations are, quantities of
HPMCK100M & Xanthan gum as independent variables (X1, X2),
and In vitro dissolution parameters such as t10%, t50% , t75% & t90%
as dependent variables. 9 formulations were prepared using 3
levels of 2 factors and all the formulations containing 40 mg of
Telmisartan were prepared as a sustained release tablet
formulation by Direct Compression technique as per the formulae
given in Table 2.
All the tablets were evaluated for different pharmacopoeial tests,
drug content, mean hardness, friability, mean thickness as per
official methods and results are given in Table 3. The hardness of
tablets was in the range of 5.127±0.409-6.068±0.413 Kg/cm2
.
Weight loss in the friability test was less than 0.44%. Drug content
of prepared tablets was within acceptance range only. Results
for all Post-compression parameters were tabulated or
summarised in Table 3.
Table 3: Post-Compression Parameters.
S.No Formulation
Code
Hardness
(kg/cm2
)
Thickness
(mm)
Friability (%) % Weight Variation Drug Content (%)
1 F1 5.252±0.428 3.98±0.125 0.259±0.07 249.42±0.139 96.84±1.6
2 F2 5.127±0.410 4.02±0.13 0.357±0.03 249.80±1.35 98.56±1.5
3 F3 5.505±0.412 4.135±0.125 0.398±0.05 251.68±1.35 100.7±1.59
4 F4 6.068±0.413 4.22±0.12 0.439±0.07 252.38±1.44 100.24±1.5
5 F5 5.94±0.394 4.28±0.125 0.361±0.025 252.85±1.4 100.89±1.4
6 F6 5.956±0.397 4.25±0.12 0.443±0.05 253.8±1.4 102.18±1.49
7 F7 6.068±0.408 4.22±0.061 0.439±0.04 252.38±1.44 100.24±1.45
8 F8 5.94±0.389 4.28±0.12 0.361±0.01 252.85±1.4 100.89±1.35
9 F9 5.956±0.392 4.25±0.115 0.443±0.02 253.80±1.45 102.18±1.44
in vitro Dissolution studies were performed for prepared tablets
using 0.1 N HCl for first two hours followed by phosphate buffer
pH 6.8 as a dissolution media at 50 rpm and temperature
37±0.5°C. The In vitro dissolution profiles of tablets were shown in
Fig.1-4 (Kinetic Plots) and the Statistical/ Kinetic (dissolution)
parameters were summarised in Table 4. Cumulative % Drug
release of Factorial Design Formulations F1-F9 at 12 Hr were
found to be in the range of 91.175-96.625 %. From the result it
reveals that the release rate was higher for formulations
containing Low level of HPMCK100M compared with other
Formulations containing Higher level, due to High concentration of
polymer drug may have entrapped within a polymer matrix
causing a decrease in rate of drug release. Therefore, required
release of drug can be obtained by manipulating the composition
of HPMCK100M and Xanthan gum.
The In vitro dissolution data of Telmisartan SR tablet formulations
was subjected to goodness of fit test by linear regression analysis
according to zero order and first order kinetic equations, Higuchi’s
and Korsmeyer-Peppas models to assess the mechanism of drug
release. The results of linear regression analysis including
regression coefficients are summarized in Table 4 and plots
shown in fig.1,2,3,4. It was observed from the above that
dissolution of majority of formulations follows First order kinetics
with co-efficient of determination (R2
) values above 0.972(0.972-
0.979). The values of r of factorial formulations for Higuchi’s
equation was found to be in the range of 0.953-0.964, which
shows that the data fitted well to Higuchi’s square root of time
equation confirming the release followed diffusion mechanism.
Kinetic data also treated for Peppas equation, the slope (n) values
ranges from 0.626- 0.887 that shows Non-Fickian diffusion
mechanism (anomalous drug transport).

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Table 4: Statistical Parameters
S.NO Formulation code
KINETIC PARAMETERS
ZERO ORDER FIRST ORDER HIGUCHI KORSMEYER-PEPPAS
a b r a b r a b r a b r
1 F1 1.917 9.223 0.98 2.116 0.1 0.979 23.907 33.888 0.957 0.626 1.392 0.992
2 F2 0.544 9.397 0.978 2.13 0.112 0.978 23.414 34.76 0.963 0.678 1.36 0.989
3 F3 0.412 9.366 0.978 2.131 0.114 0.978 2.507 34.708 0.964 0.808 1.206 0.992
4 F4 0.437 9.587 0.972 2.133 0.118 0.976 23.771 35.465 0.956 0.777 1.241 0.99
5 F5 0.833 9.748 0.971 2.16 0.135 0.975 23.292 36.259 0.96 0.828 1.206 0.989
6 F6 0.993 9.74 0.97 2.157 0.135 0.973 23.154 36.252 0.96 0.842 1.188 0.989
7 F7 0.228 9.753 0.965 2.137 0.127 0.972 23.726 36.188 0.953 0.828 1.195 0.988
8 F8 1.498 9.913 0.965 2.168 0.147 0.973 23.248 36.982 0.957 0.873 1.165 0.988
9 F9 1.658 9.906 0.964 2.165 0.146 0.973 23.11 36.975 0.957 0.887 1.148 0.987
F1 to F9 are factorial formulations, r-correlation coefficient, a-Intercept, b-Slope
Fig.1: Comparative Zero Order Plots for F1-F9
Fig.2: Comparative First Order Plots for F1-F9
Fig.3: Comparative Higuchi Plots for F1-F9
Fig.4: Comparative Korsmeyer-Peppas Plots for F1-F9
Much variation was observed in the t10%, t50%, t75% and t90% due to
formulation variables. Formulation F5 containing 37.5 mg of
HPMCK100M, 37.5 mg of Xanthan gum showed promising
dissolution parameter (t10%= 0.339 h, t50% = 2.233h, t75% = 4.466h,
t90% = 7.421h). The difference in burst effect of the initial time is a
result of the difference in the viscosity of the polymeric mixtures.
As 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 [11]. The dissolution data (Kinetic parameters) of
factorial formulations F1 to F9 were shown in Table 5.
Table 5: Dissolution Parameters of TelmisartanSR Tablets
S.No
Formulati
on
Kinetic parameters
t50%
(Hrs)
t10%
(Hrs)
t75%
(Hrs)
t90%
(Hrs)
1 F1 3.008 0.457 6.015 9.994
2 F2 2.697 0.41 5.393 8.961
3 F3 2.634 0.4 5.267 8.751
4 F4 2.551 0.388 5.101 8.476
5 F5 2.233 0.339 4.466 7.421
6 F6 2.235 0.34 4.47 7.427
7 F7 2.376 0.361 4.751 7.894
8 F8 2.052 0.312 4.104 6.819
9 F9 2.055 0.312 4.11 6.829
Polynomial equation for 3² full factorial designs is given in
Equation
Y= b0+b1 X1+b2 X2+b12 X1X2+b11 X1²+b22 X2²…
Where, Y is dependent variable, b0 arithmetic mean response of
nine batches, and b1 estimated co-efficient for factor 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
(X1X2) shows how the response changes when two factors are
simultaneously changed. The polynomial terms (X1² and X2²) are
included to investigate non-linearity. Validity of derived equations
was verified by preparing Two Check point Formulations of
Intermediate concentration (C1, C2). Polynomial equations were
derived for t10%, t50%, t75% and t90% values by backward
stepwise linear regression analysis using PCP Disso software and
Response surface plots were constructed using SIGMAPLOT V13
software.
The equations for t10%, t50% t75% and t90% developed as
follows,
Y1=0.369+0.047X1+0.0257X2+0.002X1X2+0.0197X1
2
+0.023X2
2
(For t10%)
Y2=2.427+0.309X1+0.169X2+0.013X1X2+0.131X1
2
+ 0.149 X2
2
(For t50%)
Y3=4.853+0.618X1+0.337X2+0.027X1X2+0.261X1
2
-0.298 X2
2
(For t75%)
Y4=8.064+1.027X1+0.560X2+0.045X1X2+0.434X1
2
+ 0.495X2
2
(For t90%)
The positive sign for co-efficient of X1 in Y1, Y2, Y3 and Y4
equations indicates that, as the concentration of HPMCK100M
increases, t10%, t50%, t75% and t90% value increases. In other

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Vol7 Suppl 3, July- Sep 2018 www.mintagejournals.com 26
words the data demonstrate that both X1 (amount of
HPMCK100M) and X2 (amount of Xanthan gum) affect the time
required for drug release (t10%, t50%, t75% and t90%). From the
results it can be concluded that, and increase in the amount of the
polymer leads to decrease in release rate of the drug 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 summarized in Table 6. The closeness
of Predicted and Observed values for t10%, t50%, t75% and t90%
indicates validity of derived equations for dependent variables.
S.No
Formulati
on
Kinetic parameters
t50%
(Hrs)
t10%
(Hrs)
t75%
(Hrs)
t90%
(Hrs)
1 F1 3.008 0.457 6.015 9.994
2 F2 2.697 0.41 5.393 8.961
3 F3 2.634 0.4 5.267 8.751
4 F4 2.551 0.388 5.101 8.476
5 F5 2.233 0.339 4.466 7.421
6 F6 2.235 0.34 4.47 7.427
7 F7 2.376 0.361 4.751 7.894
8 F8 2.052 0.312 4.104 6.819
9 F9 2.055 0.312 4.11 6.829
Table 6: Dissolution Parameters for Predicted And Observed
Values For Check Point Formulations
Formula
tion
Code
Predicted value Actual observed value
t10%
(h)
t50%
(h)
t75%
(h))
t90%
(h)
t10%
(h)
t50%
(h)
t75%
(h))
t90%
(h)
C1
0.3
44
2.2
61
4.5
22
7.5
14
0.3
47
2.2
73
4.5
34
7.5
28
C2
0.4
17
2.7
39
5.4
77
9.1
01
0.4
20
2.7
43
5.4
98
9.1
18
The response surface plots were presented to show the effects of
X1 and X2 on t10%, t50%, t75% and t90%. The Response surface plots
were shown in Fig.5-8 for t10%, t50%, t75% and t90% using X1 and X2 on
both the axes respectively.
Fig.5: Response surface plots for t10%
Fig.6 Response surface plots for t50%
Fig.7: Response surface plots for t75%
Fig.8: Response surface plots for t90%
The final best formulation (F4) is compared with marketed product
(TELVAS-40) shows similarity factor (f2) 90.863, difference factor
(f1) 1.665 (There is no significant difference in drug release
because tcalis<0.05). Comparative In-Vitro Dissolution profiles for
Best Formulation and Marketed Product shown in fig 9.

6. Gunda et al Mintage journal of Pharmaceutical & Medical Sciences│22-27
Vol7 Suppl 3, July- Sep 2018 www.mintagejournals.com 27
Fig.9: Comparative In-Vitro Dissolution Profile for F5 and
TELVAS-40
CONCLUSION
The present research work envisions the applicability of release
retardants such as HPMCK100M and Xanthan gum in the design
and development of sustained release tablet formulations of
Telmisartan utilizing the 32
factorial design. From the results it
was clearly understand that as the retardant (HPMC)
concentration increases the release rate of drug was retarded and
both of these polymers can be used in combination since there is
no incompatibility with the drug which may be more helpful in
achieving the desired sustained release of the drug for longer
periods. The optimized formulation followed Higuchi’s 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 F5 may
be used once a day administration in the management of
hypertension and to reduce the risk of stroke, Herat attack,
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.
ACKNOWLEDGEMENTS
The author would like to thank the Management, Principal & Staff
of M.A.M college of Pharmacy, Kesanupalli, Narasaraopet, Guntur
(D.t), A.P., India for providing support for successful completion of
research work
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