*Corresponding Author:
P. Mishra
GLA Institute of Pharmaceutical Research, 200/1, Yugal Niwas, Raman Reti, Vrindaban, Mathura
E-mail: [email protected]
Date of Submission 12 July 2006
Date of Revision 30 May 2007
Date of Acceptance 16 December 2007
Indian J Pharm Sci, 2007, 69 (6): 831-833  

Abstract

The present communication deals with the development of a new, simple, specific, sensitive, rapid and economical procedure for simultaneous estimation of atorvastatin calcium and amlodipine besylate in a combined dosage form. The method is based on the native ultraviolet absorbance maxima of the two chemotherapeutic agents. As both compounds do not interact chemically in methanol, two wavelengths 246 nm for atorvastatin calcium and 360 nm for amlodipine besylate were used. Both the drugs obeyed Beer's law in the concentration range that was employed in the method.

Keywords

Simultaneous estimation, UV spectrometric method, atorvastatin, amlodipine

Atorvastatin calcium (ATVC), [(βR,δS)-2-(4- fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3- phenyl-4[(phenylamino)carbonyl]-1H-pyrrole-1- heptanoic acid calcium salt [1-3] is a lipid lowering agent, acting through the inhibition of HMG Co-A reductase. It is used in hypercholesterolemia. Several methods for its estimation using HPLC [4,5] and HPTLC6 are reported.

Amlodipine besylate(AMLB), [3-ethyl-5-methyl (4RS)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-methyl- 1-dihydropyridine-3,5-dicarboxylate benzenesulfonate [7-9]. Amlodipine besylate is a calcium channel blocker, which is used as an antihypertensive agent. It is official in EP [10] and BP11. A number of spectrophotometric [12-17] and HPLC [18-20] methods are reported in the literature for the estimation of AMLB, both individually as well as in combination with other drugs other than ATVC.

Fixed dose combination containing ATVC and AMLB are available only in the market as tablets. To our knowledge no simultaneous method for their determination are reported. In this communication we report a new UV-spectrophotometric method for simultaneous determination of atorvastatin and amlodipine in tablets, which is simple, rapid, selective and precise.

A GBC Cintra-10 double beam UV/Vis spectrophotometer (Australia) equipped with 10 mm matched quartz cells was used in the present investigation. Methanol (AR) (Qualigens) was used in the present study. Drug samples of ATVC received from M/s Zydus Medica, Ahmedabad and AMLB from M/s IPCA Laboratories Ltd., Mumbai were used as such without further purification.

ATVC and AMLB, accurately weighed (100 mg each), were dissolved separately in 100 ml of methanol. Two milliliters of the above solutions were diluted separately to 20 ml with methanol in volumetric flask to give 100 µg/ml working standard solutions. These working standard solutions were further diluted 20 µg/ ml. These dilutions were scanned in the UV region.

ATVC showed absorption maximum at 246 nm whereas AMLB showed absorption peaks at 237 and 360 nm. ATVC has no absorbance at 360 nm. Two wavelengths selected for the formation of simultaneous equations were 246 nm and 360 nm. Both the drugs showed linearity range of 5-30 µg/ml at the selected wavelengths respectively. The absorptivity for the two drugs is presented in Table 1, while (fig. 1) represents the overlain spectra of both the drugs.

Concentration (μg/ml) AMLB Absorptivity at 246 nm AMLB Absorptivity at 360 nm
ATVC ATVC AMLB
5 5 427.00 280.60 130.00
10 10 420.10 282.40 130.90
15 15 420.13 281.40 130.40
20 20 424.35 284.70 127.45
25 25 423.64 281.28 126.32
30 30 422.43 281.20 127.43
Mean   422.94 281.93 128.75

Table 1: Absorptivity values for atorvastatin calcium and amlodipine besylate.

Figure

Figure 1: Overlain Spectra of atorvastatin calcium and amlodipine besylate

Molar absorptivity value as determined for ATVC was found to be 4.8864×104 l/mol.cm. at 246nm . Molar absorptivity values for amlodipine at 246 nm and 360 nm were 1.5988×104 l/mol.cm. and 7.3014×103 l/mol.cm, respectively. The method employs solving of simultaneous equations using Cramer’s rule and matrices. The simultaneous equations formed were, At 246 nm, A1= 0.0422 CX+0.0281 CY…1 and at 360 nm, A2= 0.0128 CY...2, where A1 and A2 are absorbances of sample solution at 246 nm and 360 nm respectively. CX and CY are the concentrations of ATVC and AMLB, respectively.

Two commercial formulations, Lipikind-Am (Mankind) and Avas-Am (Micro Labs) were purchased from a local pharmacy. The average weight of each tablet (before and after removing coating) was calculated using 20 tablets. Ten tablets were powdered finely in a glass mortar after removing the coating. Powdered sample equivalent to 100 mg of ATVC and 50 mg of AMLB of coated tablet was taken in 30 ml of methanol and shaken well to dissolve the drugs and transferred quantitatively to 100 ml volumetric flask after filtering through Whatman filter paper. The volume was then made up. Further dilutions were then accordingly made so that the final concentration lie between workable limit of 5-30 µg/ml. Absorbances of these solutions were measured at 246 nm and 360 nm and concentrations of these two drugs in the sample were calculated using Eqns. 1 and 2. Results are reported in Table 2.

Tablet Tablet component Label claim* (mg/tab) Amount found (mg/tab)* SD* % RSD* SE*
Lipikind-Am ATVC 10 9.9615 ± 0.0541 0.0677 0.6796 0.0276
  AMLB 5 5.0012 ± 0.0086 0.0109 0.2179 0.0044
Avas-Am ATVC 10 9.9637 ± 0.0448 0.0562 0.5640 0.0229
  AMLB 5 4.9861 ± 0.0217 0.0272 0.5455 0.0110

Table 2: Statistical Analysis for atorvastatin calcium and amlodipine besylate

To study accuracy, reproducibility and precision of the proposed methods, recovery studies were carried out by the addition of known amount of pure drug to the pre-analyzed sample of the tablet powder and the mixture was analyzed for the drug content using proposed method. Results of recovery studies were found to be satisfactory Table 3.

Tablet Tablet component Label claim (mg/tab)* Amount added (mg/10 tab)* Percent recovery ± SD*
Lipikind-Am ATVC 10 10 100.17 ± 0.5857
  AMLB 5 5 99.82 ± 0.1892
Avas-Am ATVC 10 10 100.11 ± 0.2871
  AMLB 5 5 99.75 ± 0.2528

Table 3: Recovery study of atorvastatin calcium and amlodipine besylate

The proposed method for simultaneous estimation of ATVC and AMLB dosage forms were found to be simple, accurate, economical and rapid. In this method, the values of coefficient of variation were satisfactorily low and recovery was close to 100 % for both the drugs. Hence, it can be employed for routine analysis in quality control laboratories.

Acknowledgements

The authors thank the Head of the Department for providing necessary facilities, and Zydus Medica, Ahmedabad, and IPCA Laboratories Ltd., Mumbai, for providing the gift samples of ATVC and AMLB, respectively. One of the authors (AG) thanks the All India Council of Technical Education (AICTE), New Delhi for providing financial assistance in the form of fellowship.

References