Simultaneous Determination of Telmisartan and Ramipril in Tablet Dosage Form by Spectrophotometry
Krishanu Pal1, M. Bhagavan Raju1, K. Pavan Kumar1, Rahul Chakravorthy2
1Dept. of Pharmaceutical Analysis and Chemistry, CM College of Pharmacy, Maisammaguda, Dhulapally Hakimpet post, Kompally, Secunderabad -500014, Andhra Pradesh India.2Dept. of Pharmaceutical Analysis and chemistry, Azad College of pharmacy, Moinabad, Shaikpet, Hyderabad
*Corresponding Author E-mail: krishanupal22@yahoo.co.in
ABSTRACT:
Two accurate, precise, sensitive and economical procedures for simultaneous estimation of Telmisartan (TEL) and Ramipril (RP) in tablet dosage form were developed. The method employed were simultaneous equation method (I), first order derivative spectroscopic method (II).The first method employs wavelength 218.94 and 295.55 nm. The second method employs wavelength 265.76 and 312.99 nm for TEL and 223.95 nm for RP. The linearity of these drugs at all the selected wavelengths for TEL is 4 -20 µg/ml, 2-10 µg/ml for RP. The concentration of these drugs was evaluated in laboratory mixture and marketed formulation. Accuracy was determined by recovery studies from tablet dosage forms and ranges form 98.67- 99.77 for Telmisartan, 97.08-101.20 for Ramipril. Precision of method was find out as repeatability day to day, and analyst to analyst variation and shows the values within acceptable limits (R.S.D<2 percent).
KEYWORDS: Telmisartan, Ramipril, Simultaneous and First order derivative method
INTRODUCTION:
Telmisartan, 4-(2-n-propyl-4-methyl-6-(1-methyl benzimidazol-2-yl)-benzimidazol-1-yl)methyl)biphenyl-2-Carboxylic acid, blocks the vasoconstrictor and aldosterone secreting effects of angiostensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
Ramipril chemically (2S, 3aS, 6aS)-1-[(S)-2-[[(S)-1-(ethoxy carbonyl)-3-phenylpropyl] amino] propanoyl] octahydro-cyclopenta[b] pyrrole-2-carboxylic acid and ramiprilate the active metabolite competes with angiotensin I for binding at the angiostensin converting enzyme , blocking the conversion of angiotensin I to angiotensin II contracts the muscles of most arteries in the body, including the heart, thereby narrowing the arteries and elevate the blood pressure.
Literature survey reveals that there are several methods like LC , RP-HPLC , HPTLC1-3 ,difference spectrometric determination of TM in tablet dosage form4 , RP-LC5 Simultaneous determination of Losartan potassium, Ramipril and Hydrochlorothiazide by HPTLC technique6,
LC-Mass spectrometry method for determination of TM in human plasma7 simultaneous spectrophotometric determination of Ramipril and Hydrochlorothiazide8, development and validation of an HPTL-densiometric method for determination of ACE inhibitors9 ,development and validation of a liquid chromatographic method for the determination of related substances of Ramipril in Altace capsules10 , spectrophotometric and atomic absorption spectrometric determination of Ramipril and perinodpil11 .several methods were reported, including spectroscopic and chromatographic methods for the individual estimation of TEL and RP or combination with other drugs. The aim of this work is to develop simple, rapid, sensitive and reliable spectrophotometric method for simultaneous estimation of TEL and RP in combined pharmaceutical dosage form. An attempt was made to develop simple, accurate, precise and economic multicomponent mode analysis method for estimation of these drugs in combined dosage forms.
MATERIALS AND METHODS:
Apparatus:
Instrument used in present study was double beam UV/Visible spectrophotometer with resolution of 1 nm and 0.5 mm slit width ( Model UV-1700,Shimazdu,Japan).All weighing was done on electronic balance (Model Shimazdu, AY-120).
Chemicals and Reagents:
Analytically pure sample of TEL and RP were provided as gift sample by Aurobindo Pharma Ltd, Hyderabad, India. The drugs were used as standards without further purification Double distilled water and sodium hydroxide pellets (AR grade) for preparation of 0.1 N sodium hydroxide were used .Commercial pharmaceutical preparation TEL TM- R 2.5 (Dr .Reddy’s Laboratories Ltd) was taken for study which contains RP-5mg and TEL-40 mg.
Preparation of standard stock solution:
TEL and RP, 100 mg of each were accurately weighed and dissolved separately in 0.1 N sodium hydroxide and made upto mark in 100 ml volumetric flask to get a concentration of 1mg/ml concentration
Preparation of working standard solution:
4 ml of TEL and 2 ml of RP standard stock solution were separately dissolved and diluted upto the mark using double distilled water in 100 ml standard flask to produce concentrations 40 µg/ml and 20 µg/ml.
Preparation of tablet sample solutions:
Accurately weighed and powdered 20 tablets of TEL and RP combination, each containing 40 mg of TEL and 2.5 mg of RP as per label claimed. A weight of 0.2765 g (Avg. wt) equivalent to 40 mg of TEL and 2.5 mg of RP was taken and dissolved in 0.1 NaOH in a 100 ml standard flask, shake well for 30 minutes and keep overnight for dissolving, subjected to sonication and filtered using Whatman filter paper and finally made up to the mark using 0.1 NaOH. The solution (Stock) prepared above contains 400 µg/ml of TEL and 25 µg/ml of RP.
METHOD DEVELOPMENT:
Method -I (Simultaneous equation method):
In this method two wavelengths in the zero order were selected such that one of the drugs shows practically nil absorbance at the detection wavelength of other drug. Water used as blank for the measurement of absorbance in simultaneous equation method. Series of dilutions of RP working standard, concentration ranging from 2-10 µg/ml were prepared and absorbances were measured at 218.94 and 295.55 nm. In the similar way series of dilutions of TEL working standard, concentration ranging from 4- 20 µg/ml were prepared and absorbance were measured at 218.94 and 295.55 nm. From the obtained absorbance values calibration curves for both the drugs were plotted separately. The absorptivity values at both the wavelengths for both the drugs were found out using calibration curves .From the absorbance values measured, the concentration of TEL and RP in the sample solution can be determined by using the simultaneous equation.
E = A/b.c …..(1)
C TEL = A2.a Y1 - A1.aY2 / aX2aY1 - ax1aY2 ….. (2)
C RP = A1.aX2 - A2. a X1 / aX2aY1 – aX2aY1 – aX1aY2 .. (3)
A1 and A2 are the absorbance of sample at 218.94 nm and 295.55 nm
ax1 and ax2 are the absorptivity of TEL at 218.94 nm and 295.55 nm
ay1 and ay2 are the absorptivity of RP at 218.94 nm and 295.55 nm
C TEL and C RP are the concentration of TEL and RP
For estimation of drug form commercial formulation, the tablet sample solution prepared were diluted to three different concentrations ranging from 80:5, 40:2.5 and 20:1.25 µg/ml of TEL and RP respectively using double distilled water. Absorbance of these solutions was measured at selected two wavelengths of 218.94 and 295.55 nm and values were substituted in the respective formulae to obtain the concentrations. The overall studies of different parameters are represented in Table-1
Method -II (First order derivative method):
The wavelengths selected for TEL and RP in first derivative mode in such a way that at one particular wavelength one drug shows some absorbance whereas the other one should show absorbance equivalent to zero. The working standards of both the drugs were scanned separately in the range 200-400 nm in D1 mode and the wavelengths selected were 265.76 and 312.99 nm for TEL and 223.95 nm for RP.A series of dilutions of mixed standards were prepared using the working solutions of both the drugs concentration ranging from 0:16, 4:12, 8:8, 12:4 and 16:0 µg/ml of TEL and RP respectively and D1 values were measured at selected wavelengths. From the obtained D1 values calibration curves for both the drugs were plotted separately.
For estimation of drug from commercial formulation, the tablet samples solution prepared were diluted to three different concentrations ranging 80:5, 40:2.5 and 20:1.25 µg/ml of TM and RP respectively using double distilled water. D1 of these solutions were measured at selected wavelengths of 223.95 nm for RP and 265.76 and 312.99 nm for TEL, and D1 values were used to calculate the concentration of both the drugs.
RESULTS AND DISCUSSION:
The proposed spectrophotometric method was found to be simple, accurate, economical, precise and rapid for routine analysis of simultaneous estimation of TM and RP in combined solid dosage form. These methods were successfully used for estimation of both the drug in combined tablet formulation. The overall studies of different parameters of simultaneous equation method are summarized in Table-1 and the overall studies of different parameters of first order derivative method are summarized in Table-2.Overlain spectrum showing linearity of mixed standards (simultaneous equation method) for TEL and RP are represented in Fig-1.The overlain first derivative spectra of TEL and RP are showing linearity of TEL and RP in mixed standard is represented in Fig-3. On observing the validation parameters, both the methods were found to be precise, accurate and specific. Hence, the proposed methods can be employed for routine assay of tablets containing TM and RP.
Table 1: Overall study of different parameters of simultaneous Equation method
|
Parameters |
Telmisartan |
Ramipril |
Acceptance Limit |
|
|
Absorptivity values |
218.94 nm |
1108.09 |
246.46 |
- |
|
295.55 nm |
525.73 |
- |
||
|
Linearity Range |
4 - 20 |
2 - 10 |
- |
|
|
Correlation Coefficient |
0.9998 |
0.9998 |
0.9960 |
|
|
System Precision ( % RSD ) |
0.109168 |
0.285771 |
< 2 |
|
|
Method Precision ( % RSD ) |
0.489183 |
0.015166 |
< 2 |
|
|
LOD |
0.0572 |
0.0849 |
- |
|
|
LOQ |
0.1693 |
0.2574 |
- |
|
|
Assay ( % Purity ) |
97.02 – 98.35 |
97.08 – 101.20 |
97 - 103 |
|
|
% Recovery |
98.67 – 99.77 |
97.18 – 101.60 |
97 - 103 |
|
|
Parameters |
Results |
Acceptance Criteria |
||
|
Telmisartan |
Ramipril |
|||
|
Detection Wavelength |
265.76 nm |
312.99 nm |
223.95 nm |
- |
|
Linearity Range ( µg/ml ) |
0 – 16 |
0 – 16 |
0 – 16 |
- |
|
Correlation Coefficient |
0.9996 |
0.9996 |
0.9988 |
0.9960 |
|
Slope |
0.2068 |
0.3706 |
0.3756 |
- |
|
Intercept |
0.2389 |
0.0066 |
0.7946 |
- |
|
LOD |
0.0646 |
0.0310 |
0.0849 |
- |
|
LOQ |
0.1959 |
0.0941 |
0.2572 |
- |
|
System Precision ( % RSD ) |
0.15718 |
0.15934 |
0.15913 |
<2 |
|
Method Precision ( % RSD ) |
1.7766 |
1.6990 |
2.3442 |
<2 |
|
Assay ( % Purity ) |
98.37 – 99.31 |
97.78 – 99.24 |
97.00 – 98.72 |
97-103 |
|
Percentage Recovery |
98.96 – 100.46 |
98.31 – 100.05 |
97.07 – 98.79 |
97-103 |
Table 2: Overall study of different parameters of first order Derivative method
Fig-1Overlain Spectrum showing linearity for TEL and Fig-2 : First derivative overlain spectrum showing linearity of
RP(simultaneous equation method) TM and RP in mixed standard
Figure 3: Assay Overlain Spectrum of Telmisartan-Ramipril Figure 4: Overlain Absorbance Spectrum of Telmisartan-Ramipril
Marketed. Formulation in absorbance mode in recovery studies
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Received on 19.02.2010 Modified on 07.03.2010
Accepted on 20.03.2010 © RJPT All right reserved
Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 861-864