International Invention Journal of Biochemistry and Bioinformatics (ISSN: 2408-722X) Vol. 3(1) pp.

5-13, January, 2015

Available online http://internationalinventjournals.org/journals/IIJBB
Copyright ©2015 International Invention Journals

Full Length Research Paper

Stability indicating HPTLC method for simultaneous

estimation of Cilnidipine and Telmisartan in their
combined dosage form
Shahin I.Vahora*, Falgun A. Mehta,Usmangani K. Chhalotiya, Dimal A. Shah, Kashyap K.
Bhatt.
IndukakaIpcowala College of Pharmacy, Beyond GIDC, P.B. No. 53, VitthalUdyognagar- 388 121, Gujarat, India.

Abstract

A sensitive, selective and precise high performance thin layer chromatographic method has been
developed and validated for the simultaneous estimation of Cilnidipine and Telmisartan both as a bulk
drug and in formulation. The method employed HPTLC aluminum plates pre-coated with silica gel
60F-254 as the stationary phase while the solvent system was chloroform: methanol: toluene (6:0.7:2
v/v/v). The Rf values of Cilnidipine and Telmisartan were observed to be 0.59 and 0.30 respectively.
The densitometric analysis was carried out in absorbance mode at 254 nm. The linear regression
analysis data for the calibration plots showed a good linear relationship for Cilnidipine and
Telmisartan over a concentration range of 100-600 ng/spot and 400-2400 ng/spot respectively. The
method was validated for precision, robustness and % recovery. The limit of detection and limit of
quantification for Cilnidipine and Telmisartan were found to be 14.95 and 10.37 ng/spot, 45.32 and
31.43 ng/spot respectively. Statistical analysis showed that the method is repeatable, selective and
precise. Cilnidipine and Telmisartan were subjected to acid, base, peroxide and UV-induced
degradation. In stability tests the drugs were susceptible to acid and basic hydrolysis, oxidation and
photodegradation. Statistical analysis proved the method is repeatable, selective, and accurate for
estimation of Cilnidipine and Telmisartan. Because the method could effectively separate the drugs
from their degradation products, it can be used as a stability-indicating method.

Keywords: Cilnidipine,Telmisartan, HPTLC, Validation, Stability indicating and validation.

INTRODUCTION

Cilnidipine (CIL) is a light yellowish powder. Chemically it benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1-

is 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5- yl)methyl)biphenyl-2-carboxylic acid (Löhn et al., 2002;
pyridinedicarboxylic acid 2-methoxyethyl(2E)-3phenyl-2- Indian Pharmacopoeia, 2007) (Figure 1b).
prpenyl ester (Löhn et al., 2002 )(Figure 1a). It is very soluble in methanol and practically
It is antihypertensive agent and calcium channel insoluble in water. It is Angiotensin-converting Enzyme
blocker. Cilnidipine is a dual L-/N-type calcium Inhibitors and Angiotensin II Type 1 Receptor Blockers
channel protein inhibitor and blocker. Cilnidipine has agents. The mechanism by which Telmisartan is an
displayed renal and vascular protective effects and angiotensin II receptor blocker (ARB) that shows high
improved baroreflex sensitivity in patients with affinity for the angiotensin II receptor type 1 (AT1), with a
hypertension. Telmisartan (TEL) is white crystalline binding affinity 3000 times greater for AT1 than AT2. It
powder. Chemically, it is 4′-((4-Methyl-6-(1-methyl-1H- has the longest half-life of any ARB (24 hours) and the
largest volume of distribution (Löhn et al., 2002). The
combination of CIL and TEL is indicated as
antihypertensive agents. (Lee et al., 2010)
Literature survey revealed that Cilnidipine can be
*Corresponding Author Email: shahin121190@gmail.com; Tel: estimated by spectrophotometry ( Safi, 2013; Chaudhri
+91-02692-229520
6 Int. Inv. J. Biochem. Bioinform.

Figure 1a. Cilnidipine Figure 1b. Telmisartan

and Bhalerao, 2012; Safhi and Yagaina, 2013) and by aluminum plate 60 F254, (10 cm x 10 cm with 0.2 mm
liquid chromatographic methods (George, 2005; Lee et thickness, E. Merck, Germany). Camag TLC scanner
al., 2012; Zhang et al., 2007) individually or in was used for the densitometric scanning of the
combination with other drugs, and Telmisartan can be developed chromatogram. All the drugs and chemicals
estimated by spectrophotometry (Sharma et al., 2012; were weighed on Mettlortoledo electronic balance.
Tatane, 2011; Pandey et al., 2011; Rathod et al., 2012;
Palled et al., 2006) and by liquid chromatographic
methods individually or in combination with other drugs Chemicals and Reagents
(Surekha et al., 2012; Rao et al., 2013; Kumar et al.,
2011). Two methods UV spectroscopy (Haripriya et al., Analytically pure CIL and TEL were obtained as gratis
2013) , RP-HPLC (Pawar et al., 2013) have been samples from J.B Chemicals and Pharmaceuticals,
reported for the estimation of Cilnidipine and Telmisartan Daman India and Akums Drugs and Pharmaceuticals
in their combined dosage form. The reported methods limited, Hardwar India respectively. AR grade methanol,
are highly sophisticated, costly, time-consuming and chloroform and toluene were procured from Sisw
require special sample preparation. HPTLC method is Research.lab, Mumbai, India, Astron chemicals,
considered to be a good alternative, and it should be Ahmedabad, India and Chiti-Chem Corporation, Baroda,
widely explored as an important tool in routine drug India respectively. Tablet formulation (CILACAR T, J.B
analysis. chemicals and pharmaceuticals Ltd., Mumbai, India)
Present study involves development of a high containing labeled amount of 10 mg of cilnidipine and 40
performance thin layer liquid chromatographic method mg of telmisartan were purchased from local market.
for the determination of CIL and TEL in combination
dosage form.A major advantage of HPTLC is its ability to
analyze several samples simultaneously using a small Chromatographic System
quantity of mobile phase. This reduces the time and cost
of analysis, minimizes exposure risks, and significantly Sample Application
reduces disposal problems of toxic organic solvents,
thereby reducing the possibilities of environment Standards and formulation samples of CIL and TEL were
pollution. applied on the HPTLC plates in the form of narrow
The aim of the present work was to develop an bands of 8 mm length and with 9 mm distance between
accurate, repeatable, and specific HPTLC method for two bands. Samples were applied under a continuous
the determination of CIL and TELboth as a bulk drug and drying stream of nitrogen gas.
in formulation in the presence of their degradation
products, as stipulated by the ICH guidelines. The
proposed method was validated according to ICH Mobile Phase and Development
guidelines (ICH, 1996 and 2005) and its updated
international convention. Plates were developed using a mobile phase consisting
of chloroform: methanol: toluene (6:0.7:2 v/v/v). Linear
ascending development was carried out in a twin-trough
Experimental glass chamber equilibrated with the mobile phase vapors
for 15 min at ambient temperature. Ten milliliters of the
HPTLC Instrument mobile phase (5 mL in the trough containing the plate
and 5 mL in the other trough) was used for each
The samples were applied with a sample syringe development and was allowed to migrate a distance of
(Hamilton, Switzerland) using CamagLinomat 5 80 mm. After development, the HPTLC plates were
(Switzerland) sample applicator on pre-coated silica gel dried.
 Vahora et al. 7

Densitometric Analysis interday precisions. Intraday precision were determined

by analyzing sample solutions of CIL and TEL at three
Densitometric scanning was performed in the levels covering low, medium, and high concentrations of
absorbance mode under control by winCATS planar the calibration curve three times on the same day (n =
chromatography software (ver.4.2). The source of 3). Interday precision was determined by analyzing
radiation was the deuterium lamp, and bands were sample solutions of CIL and TEL at three levels covering
scanned at 254 nm. The slit dimensions were 6 mm low, medium, and high concentrations over a period of 3
length and 0.45 mm width, with a scanning rate of 20 days (n = 3). The peak areas obtained were used to
mm/s. Concentrations of the compound chromatographic calculate mean and RSD values.
were determined from the intensity of diffusely reflected Repeatability of measurement of peak area were
light and evaluated as peak areas against determined by analyzing CIL and TEL sample seven
concentrations using a linear regression equation. times without changing the position of plate.

Preparation of Standard Stock Solution Sensitivity

Stock solutions were prepared by accurately weighing Sensitivity of the method was determined with respect to
25 mg of CIL and 25 mg of TEL transferring to 25 mL LOD and LOQ. Noise was determined by scanning a
volumetric flask containing a few mL of methanol. The blank band (methanol) six times. A series of
flask was swirled and sonicated for few minutes to concentrations of drug solutions for CIL 100-600
dissolve the solids. Volume was made up to the mark ng/band and for TEL400-2400 ng/band were applied on
with methanol to yield a solution containing 1000 g/mL a plate and analyzed to determine LOD and LOQ. LOD
of CIL and TEL, respectively. Aliquot from the stock was calculated as 3.3 times the noise level, and LOQ
solution of CIL and TEL were appropriately diluted with was calculated as 10 times the noise level. LOD and
methanol to obtain working standard solution of 100 LOQ were experimentally verified by diluting the known
g/mL of CIL and TEL respectively. concentrations of CIL and TEL until the average
responses were approximately 3–10 times the SD of the
responses for six replicate determinations.
Validation

Validation of developed HPTLC method was done with Robustness

respect to following parameters.
Small changes in the chamber saturation time, and
change in mobile phase, and the effects on the results
Linearity of Calibration Curves were examined. Robustness of the method were
determined in triplicate at a concentration level of 400
Linearity of the method was determined by constructing
ng/band for CIL and 1600 ng/band for TEL, and the
calibration curves at six concentration levels over a
mean and RSD of peak areas were calculated.
range of 100-600 ng/band for CIL and 400-2400 ng/band
for TEL. The calibration curves were developed by
plotting peak area versus concentration (n = 6) with the Analysis of Marketed Formulations
help of the winCATS software.
Twenty tablets were weighed accurately and finely
Accuracy powdered. Tablet powder equivalent to 10mg of CIL and
40 mg of TEL were accurately weighed and transferred
The accuracy of the method was determined by to a 10 mL volumetric flask. A few mL (5 mL) of
calculating recoveries of CIL and TEL by method of methanol was added to the above flask and flask was
standard additions. Known amount of CIL (0, 80, 100, sonicated for 5 min. The solution was filtered using
120 ng/spot) and TEL (0, 80, 100, 120 ng/spot) were Whatman filter paper No.1 in another 10 mL volumetric
added to a pre quantified sample and the amount of CIL flask and volume was diluted to the mark with the
and TEL were estimated by measuring the peak area methanol. 1 mL aliquot from the above solution was
and by fitting these values to the straight-line equation of taken in 10 mL volumetric flask and diluted to mark with
calibration curve. methanol to obtain final concentration of 100 μg/mL for
CIL and TEL was obtained. The possibility of
interference from other components of the tablet
Precision formulation in the analysis was studied. From the
developed chromatogram spot area and Rf values were
Precision was evaluated in terms of intraday and determined.
8 Int. Inv. J. Biochem. Bioinform.

Forced Degradation of CIL and TEL appropriate Rf value for CIL and TEL were desired.
Various mobile phases such as methanol–ethylacetate,
Acid Catalyzed Induced Degradation chloroform-methanol, methanol – ethyl acetate-toluene,
were evaluated in different proportions. A mobile
To 1 ml of working standard solutions of Cilnidipine and consisting of chloroform: methanol: toluene(6:0.7: 2,
Telmisartan separately, each of conc. 1000 µg/ml, 2 ml v/v/v) gave good separation of CIL and TEL from its
of 0.5 N HCl was added and kept at room temperature matrix. It was also observed that chamber saturation
for 1 hour.(Initially 0.1N was taken at room temperature time and solvent migration distance were crucial in the
for 1hour and gradually increase the time like 3,6 hour chromatographic separation as chamber saturation time
and strength and finally degraded in 0.5 N) The solutions of less than 15 min and solvent migration distances
were diluted to 10 ml with methanol. Appropriate volume greater than 80 mm resulted in diffusion of the analyte
of resultant solution was applied on TLC plate (300 band. Therefore, chloroform: methanol: toluene (6:0.7: 2,
ng/spot and 1200 ng/spot of Cilnidipine and Telmisartan v/v/v) mobile phase with a chamber saturation time of 15
respectively.) and densitograms were analyzed. min at 25 0C and solvent migration distance of 80 mm
was used. These chromatographic conditions produced
a well-defined, compact band of CIL and TEL with
Degradation under Alkali Catalyzed Hydrolytic optimum migration at Rf0.59 and 0.30 respectively
Condition (Figure 2).

To 1 ml of working standard solutions of Cilnidipine and

Telmisartan separately, each of conc. 1,000 mcg/ml, 2 Validation
ml of 0.5 N NaOH was added and kept at room
temperature for 1 hour. The solutions were diluted to 10 Linearity and calibration curves
ml with methanol. Appropriate volume of resultant
solution was applied on TLC plate (300 ng/spot and Linearity of an analytical method is its ability, within a
1200 ng/spot of Cilnidipine and Telmisartan given range, to obtain test results that are directly, or
respectively.) and densitograms were analyzed. through a mathematical transformation, proportional to
the concentration of the analyte. The method were found
to be linear in a concentration range of 100-600 ng/band
Degradation under Oxidative Conditions (n = 6) for CIL and 400-2400 ng/band (n= 5) for TEL with
respect to peak area. Figure 3 displays a three-
To 1 ml of working standard solutions of Cilnidipine and dimensional overlay of HPTLC densitograms of the
Telmisartan separately, each of conc. 1000 mcg/ml, 2 ml calibration bands of CIL and TEL at 254 nm. The
of 12% H2O2 was added and kept at room temperature regression data shown in Table 1 reveal a good linear
for 1 hour. The solutions were diluted to 10 ml with relationship over the concentration range studied,
methanol. Appropriate volume of resultant solution (300 demonstrating the suitability of the method for analysis.
ng/spot and 1200 ng/spot of Cilnidipine and Telmisartan
respectively) was applied on TLC plate and
densitograms were analyzed. Accuracy

Accuracy of an analytical method is the closeness of test

Photo-Degradation Studies results to the true value. It was determined by the
application of analytical procedure to recovery studies,
Photolytic degradation studies were carried out by where a known amount of standard is spiked into pre-
exposure of drugs to UV light up to illumination of 200 analyzed samples solutions. Results of the accuracy
watt hours/square meter and subsequently cool studies from excipients matrix are shown in Table 2;
fluorescent light to achieve an illumination 1.2 million recovery values demonstrated the accuracy of the
Lux.Hr. (ICH, 1996). method in the desired range.

RESULTS AND DISCUSSION Precision

Optimization of the Mobile Phase The precision of an analytical method expresses the
degree of scatter among a series of measurements
To develop the HPTLC method of analysis of CIL and obtained from multiple sampling of the same
TEL for routine analysis, selection of the mobile phase homogeneous sample under prescribed conditions.
was carried out on the basis of polarity. A mobile phase Intraday precision refers to the use of an analytical
that would give a dense and compact band with an procedure within a laboratory over a short period of time
 Vahora et al. 9

Figure 2. Densitogram of CIL and TEL using mobile phase chloroform: methanol: toluene(6:0.7:2 v/v/v)

Figure 3.Three dimensional overlay of HPTLC densitograms of calibration bands of CIL

Table 1. Regression Analysis of Calibration Curve

Parameters CIL TEL

Linearity range (ng/spot) 100-600 800-2400
Slope 7.66 1.943
Standard deviation of slope 0.116432 0.005263
Intercept 395.6 1026.6
Standard deviation of intercept 34.71868 6.107373
Correlation coefficient 0.997 0.996
10 Int. Inv. J. Biochem. Bioinform.

Table 2. Summary of validation parameters

Parameters CIL TEL

Rf 0.59 0.30
Detection limit (ng/spot) 14.95 10.37
Quantitation limit (ng/spot) 45.32 31.43
Accuracy (%) 99.4-100.09% 100.7-101.1%
Precision (RSD, %)
 Intra-day precision (n=3) 0.66 – 1.37% 0.18-1.01%
 Inter-day precision (n=3) 0.72-1.15% 0.19-0.36%
Repeatability study (%RSD) (n=6) 0.96 % 0.22%

Table 3. Robustness Studies

Parameters Normal Change in condition Change in % RSD

condition CIL TEL
Chamber Saturation time 20 min 18 min 0.47 0.31
22 min 1.04 0.66
Mobile phase ratio 6:0.7:2 6:0.5:2.5 0.86 0.57
7:0.7:3 1.15 1.00

by the same operator with the same equipment, whereas resolved band at Rf 0.59and 0.30were observed in the
interday precision involves estimation of variations in chromatogram of CIL and TEL, and no interference from
analysis when a method is used within a laboratory on the excipients present in the marketed tablet formulation
different days. The results obtained are shown in Table was observed.
2. In all instances, RSD values were less than 5%,
confirming the precision of the method. Repeatability of
the scanning device was studied by applying and Degradation Behavior
analyzing CIL sample (400 ng/spot) and TEL sample
(1600 ng/spot) seven times. RSD was less than 5% HPTLC studies on CIL and TEL under different stress
(Table 2), which was well below the instrumental conditions suggested following degradation behavior.
specifications.

Hydrolytic Studies
Limit of Detection and Limit of Quantification
Acidic Condition
Under the experimental conditions used, the lowest
amount of CIL and TEL that could be detected (LOD) Drugs, CIL and TEL showed 25.4% and 38.9%
were found to be 14.95 ng/spot and 10.37 ng/spot, and degradation under acidic hydrolysis at room temperature
the lowest amount of CIL and TEL that could be respectively. Additional peaks were observed for CIL at
quantified (LOQ) were45.32ng/spot and 31.43 ng/spot. Rf 0.44 and for TEL at 0.06,0.1 and 0.29 respectively.
(Figure 4).

Robustness
Alkaline condition
The low values of RSD (Table 3) obtained after
introducing small, deliberate changes in parameters of CIL degraded under alkaline condition (2 ml of 0.5N
the developed HPTLC method confirmed its robustness. NaOH) in short period of time. Three new peaks were
observed for product of CIL formed under these
conditions at Rf 0.45,0.49 and 0.57. CIL and TEL
Analysis of marketed formulation degraded to about 13.1% and 63.11% under alkaline
condition (2 ml of 0.5N NaOH) after keeping for 1 hour.
Marketed formulation was analyzed using proposed One peak was observed for degradation product of CIL
method which gave percentage recoveries of 99.4- at Rf0.44 and for TEL three peaks were observed at Rf
100.09% for CIL and 100.7-101.1% for TEL. A well 0.07, 0.1 and 0.32. (Figure 5).
 Vahora et al. 11

Figure 4. Densitogram of mixture in HCl degradation

Figure 5. Densitogram of mixture in NaOH degradation

Oxidative Studies stability of drugs upon exposure to white fluorescent light

and UV light for specified period. The forced degradation
CIL and TEL showed 15.7% and 39.54% degradation study results are summarized in Table 4. (Figure 7).
upon treatment with 12% H2O2 at room temperature.
Reduction in area of peak of CIL was observed and
three other peaks of degraded product were found at Rf CONCLUSION
0.45, 0.49 and 0.57 and for TEL one peak of degraded
product was observed at Rf 0.16 upon treatment with Introducing HPTLC method in pharmaceutical analysis
12% H2O2 at room temperature. (Figure 6). represents a major step in quality assurance. A specific,
accurate and precise HPTLC analytical method has
been developed for the simultaneous estimation of
Photolytic Studies Cilnidipine and Telmisartan as bulk and in
pharmaceutical formulation. From the above study, we
Under photolytic studies, additional peaks were can conclude that the CIL and TEL undergo degradation
observed of CIL at Rf 0.49 and two peaks were to different extent under different, above mentioned,
observed of TEL at Rf 0.12 and 0.2. This indicates stress conditions. In this study, the products formed after
12 Int. Inv. J. Biochem. Bioinform.

Figure 6. Densitogram of mixture in H2O2 degradation

Figure 7. Densitogram of mixture in photo degradation

Table 4. Degradation Studies

Sample exposure conditions No. of degradation products (Rf) Drug remained % degradation
(ng)
CIL TEL CIL TEL CIL TEL
0.5N HCl,1 hr,RT 1 3 223.8 733.2 25.4 38.9
(0.44) (0.06,0.1,0.29)
0.5N NaOH,1 hr,RT 1 3 260.7 442.6 13.1 63.11
(0.44) (0.07,0.1,0.32)
12% H2O2,1 hr,RT 3 1 252.9 725.5 15.7 39.54
(0.45,0.49,0.57) (0.16)
Photo degradation,12 hr 1 2 196.8 929.2 34.4 22.56
(0.49) (0.12,0.2)
 Vahora et al. 13

forced decomposition studies were resolved from the Lee KR, Chae YJ, Lee JH, Kim DD, Chong S, Shim CK, Chung SJ
(2012). Quantification of Cilnidipine in Human Plasma byLC-MS.
bulk drug response. From the peak purity profile studies, journal of liquid chromatography and related technologies.35, 308-
it was confirmed that the peak of the degradation 320.
product was not interfering with the response of drugs. It Löhn M, Muzzulini U, Essin K, Tsang S, Kirsch T, Litteral J, Waldron P,
confirms that degradation product of drug can be Conrad H, Klugbauer N, Hofmann F, Haller H, Luft F, Huang Y,
separated from the drug by this method. The developed Gollasch M (2002). Cilnidipine Is A Novel Slow-Acting Blocker Of
Vascular L-Type Calcium Channels That Does Not Target Protein
method is simple, accurate, precise, and specific. It is Kinase C.May , 20 (5), 885–
proposed for routine analysis of these drugs in the 93. http://en.wikipedia.org/wiki/Cilnidipine.
presence of degradation products in stability study. Palled MS, Chatter M, Rajesh PMN, Bhatt AR (2006). Difference
Spectrophotometric Determination Of Telmisartan In Tablet Dosage
Statistical analysis proves that the method is suitable for Forms. Indian journal of of pharmaceutical science.68, 685-686.
the analysis of Cilnidipine and Telmisartan as a bulk Pandey A, Sawarkar H, Singh M, Kashyap P, Gosh P (2011). UV
drug and in pharmaceutical formulation without any Spectrophotometric Method For Estimation Of Telmisartan In Bulk
interference from the excipients.The method was And Tablet Dosage Form. International journal of chemtech research.
3, 657-660.
successfully validated in accordance with ICH Pawar P, Gandhi SV, Deshpande PB, Vanjari S, Shelar SU (2013).
guidelines.The method can be used to determine the Simultaneous RP-HPLC Estimation Of Cilnidipine And Telmisartan In
purity of drug available from various sources. Combined Tablet Dosage Form.Pelagia research library.4, 6-10.
Rao JS, Vijayasree V, Palavan CA (2013). Validated RP-HPLC Method
For The Estimation Of Telmisartan In The Tablet Dosage
Form.American journal of pharmatech research.
ACKNOWLEDGEMENTS Rathod SD, Patil PM, Santosh SA, Chaudhri PD (2012). UV
Spectroscopic Method For Estimation Of Telmisartan In Bulk And
Authors are grateful to J B Chemicals and Tablet Dosage Form.Indianjournal of pharmaceutical science and
research.3, 3936-3939.
Pharmaceuticals, Daman and Akums Drugs and
Safhi MM, Yagaina NM (2013). Development And Validation Of A
Pharmaceuticals limited, Hardwar for providing gift Rapid Stability Indicating Chromatographic Determination Of
sample of standard Cilnidipine and Telmisartan Cilnidipine In Bulk And Dosage Form.Indian journal.com.6, 296-299.
respectively. The authors are very thankful to director of Safi M (2013). Spectrophotometric Method For The Estimation For
Cilnidipine In Bulk And Pharmaceutical Dosage Forms.Oriental
SICART and principal of IndukakaIpcowala College of
journal of chemistry. 29, 131-134.
Pharmacy, New VallabhVidyanagar, for providing Sharma RK, Chippa RC, Singh R, Alam I (2012). Quantitative
necessary facilities to carry out research work. Estimation Of Telmisartan In Bulk Drug And Tablets By
UvSpectroscopy. International Journal of Drug Research and
Technology.2 , 268-272.
Surekha ML, Kumara Swamy G, Ashwini GL (2012). Development And
REFERENCES Validation Of RP-HPLC Method For Estimation Telmisartan In Bulk
And Tablet DosageForm.Internation journal of drug development
Chaudhri PP, Bhalerao AV (2012). Method Validation For and research.4,200-205.
Spectrophotometric Determination OfCilnidipine.International journal Tatane S (2011). Development of Spectrophotometric Determination of
of Pharmacy and pharmaceutical science,4, 96-98. Telmisartan in Tablet Dosage Form. Journal of advances in pharmacy
George L (2005). HplcMethods For Recently Approved and healthcare research.23-26.
Pharmaceuticals. Wiley Interscience.155. Zhang X, Zhai S, Zhao R, Ouyang J, Li X, Baeyens WR (2007).
Haripriya M, Neethu A, Jayasekhar P (2013). Development And Determination Of Cilnidipine, A New Calcium Antagonist, In Human
Validation Of Uv Spectrophotometric Method For The Simultaneous Plasma Using High Performance Liquid Chromatography With
Estimation Of Cilnidipine And Telmisartan In Tablet Dosage Form Tandem Mass Spectrometric Detection.Analchemacta.26, 142-146.
Utilising Simultaneous Equation And Absorbance Ratio
Method.International journal of pharmacy and biological
science.3,343-348.
Indian Pharmacopoeia (2007). Govt. of India, The Indian
pharmacopoeia commission, Ghaziabad, Ministry of Health & Family
welfare, vol-2, pp2186-2187.
International Conference on Harmonization (ICH) (1996). Stability
Testing: Photostability Testing of New Drug Substances and Products How to cite this article: Vahora SI, Mehta FA, Chhalotiya UK, Shah
(Q1B). In ProceedingsIFPMA: Geneva. DA, Bhatt KK (2015). Stability indicating HPTLC method for
International Conference on Harmonization, Food and Drug simultaneous estimation of Cilnidipine and Telmisartan in their
Administration (ICH) (1996 and 2005).Validation of Analytical combined dosage form. Int. Inv. J. Biochem. Bioinform. 3(1):5-13
Procedures:Methodology (Q2R1)), USA.
International Conference on Harmonization, Food and Drug
Administration, (ICH), Q1A (1993). Stability testing of new drug
substances and products, International Conference on
Harmonization,Geneva, Switzerland, October.
Kumar GV, Murthy TEGK, Rao KRS (2011).Validated Rp-Hplc Method
For The Estimation Of Telmisartan In Serum Samples. International
Journal Of Research In Pharmacy And Chemistry. 1,703-706.
Lee KH, Park HJ, Shim C, Myung C (2010). patent on “Pharmaceutical
Composition Comprising Cilnidipine And Telmisartan”
WO2010047453 A1.