Rajiv Gandhi University of Health Sciences, Karnataka Bangalore.

“DEVELOPMENT AND VALIDATION OF NEW ANALYTICAL METHODS FOR THE SIMULTANEOUS ESTIMATION OF AMLODIPINE BESYLATE AND LISINOPRIL IN BULK DRUG AND PHARMACEUTICAL FORMULATIONS”

A Protocol submitted to Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.

In partial fulfillment of the requirement for the award of

MASTER OF PHARMACY

IN

PHARMACEUTICAL ANALYSIS

BY

VENKATA SAI DEEPTHI.K

MAY-2011

Department of Pharmaceutical Analysis,

National College of Pharmacy,

Balraj Urs Road,

Shimoga-577 201,

Karnataka, INDIA.

Rajiv Gandhi University of Health Sciences, Karnataka Bangalore.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the candidate and address: / Ms. Venkata Sai Deepthi.K
Department of Pharmaceutical Analysis,
National College of Pharmacy,
Balraj Urs Road,
Shimoga-577201.
Permanent address
Venkata Sai Deepthi.K,
D/o K.V.Rathnam,
Kothapeta,
Rapur,
Nellore-District.
Andhrapradesh.Pin-524408.
2. / Name of the institution: / National College of Pharmacy,
Balraj Urs Road,
Shimoga-577201.
3. / Course of study and subject: / MASTER OF PHARMACY IN
PHARMACEUTICAL ANALYSIS
4. / Date of admission: / 04/10/2010
5. / Title of the topic:
“DEVELOPMENT AND VALIDATION OF NEW ANALYTICAL METHODS FOR THE SIMULTANEOUS ESTIMATION OF AMLODIPINE BESYLATE AND LISINOPRIL IN BULK DRUG AND PHARMACEUTICAL FORMULATIONS”

6. BRIEF RESUME OF THE INTENDED WORK:

6.1 Need for the study:

Amlodipine besylate is a long-acting calcium channel blocker (dihydropyridine derivative) used as an anti-hypertensive and in the treatment of angina1. Like other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing total peripheral resistance and hence reducing blood pressure, in angina it increases blood flow to the heart muscle2. It is a official drug in IP3 and BP4. Few bioanalytical methods by HPLC using human plasma and also spectrophotometric methods using pharmaceutical dosage forms have been reported for the estimation of Amlodipine besylate.

Lisinopril is an angiotensin-converting enzyme(ACE) inhibitor used to treat high blood pressure (hypertension), congestive heart failure and chronic renal failure. Lisinopril inhibits angiotensin-converting enzyme (ACE) and reduces the angiotensin II levels which leads to the reduction of aldosterone secretion thus lowering of blood pressure5. It is an official drug in IP and BP. There are very few analytical methods reported for the estimation of Lisinopril which includes RP-HPLC, Spectrophotometry and fluorimetry.

The combination of Amlodipine besylate and lisinopril is very useful in the treatment of hypertension. On literature survey, it was found that only simultaneous equation method has been reported for the simultaneous estimation of Amlodipine besylate and Lisinopril in combined dosage forms and no method is available in the pharmacopoeias. In view of the need for suitable methods for routine analysis in combined formulations, attempts are being made to develop simple, precise and accurate analytical methods for simultaneous estimation of titled drugs and extend it for their determination in formulations. As chromatographic methods of analysis is a pre-requisite for the marketing of most of the formulations, one HPLC and HPTLC along with Spectrophotometric methods such as First order derivative method, Area under the curve method and Q-ratio method are planned to develop and validate for the simultaneous estimation of titled drugs, using methanol as solvent.

DRUG PROFILE

AMLODIPINE BESYLATE6,7

.

IUPAC Name : 2-[(2-Aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine benzenesulfonate

Molecular formula : C26H31ClN2O8S.

Molecular weight : 567.05 g/mol.

Description : It is a White Crystalline powder.

Solubility : Freely soluble in Methanol, Slightly soluble in Water & Sparingly

Soluble in Ethanol

Category : Antihypertensive drug

LISINOPRIL6,7 (ANHYDROUS)

IUPAC Name : (S)-1[(N2 – (1-carboxy-3-phenyl propyl)-L-lysyl]-L-proline.

Molecular formula : C21H31N3O5.

Molecular weight : 405.4g/mol

Description : It is white crystalline powder

Solubility : Soluble in water and methanol, partially insoluble in

acetone and ethanol. Category : Antihypertensive drug

6.2  REVIEW OF LITERATURE:

·  Meyyanathan SN, et al;8 developed a simple sample preparation with HPLC-UV method for estimation of Amlodipine from plasma: Application to bioequivalence study.

·  Yuanyuan M, et al;9 reported Determination and pharmacokinetic study of Amlodipine in human plasma by ultra performance liquid chromatography-electrospray ionization mass spectroscopy.

·  Rahman N, et al;10 developed Applications of oxidants to the spectrophotometric determination of Amlodipine besylate in pharmaceutical dosage forms.

·  Rahman N, et al;11 validated Spectrophotometric methods for the determination of Amlodipine besylate in drug formulations using 2,3dichloro5,6dicyano1,4 benzoquinone and ascorbic acid.

·  Dhabale PN, et al;12 reported Development and statistical validation of UV spectrophotometric method for estimation of Amlodipine besylate in tablet dosage form.

·  Divya kanth, et al;13 reported RP-HPLC methods for development and validation of Lisinopril tablets.

·  Basaviah K, et al;14 developed Spectrophotometric determination of Lisinopril in pharmaceuticals using Ninhydrin-a modified approach.

·  Raza A, et al,15 reported Spectrophotometric determination of Lisinopril in pure and pharmaceutical formulations.

·  Jamakhandi CM, et al;16 have developed New fluorimetric method of determination for Lisinopril dosage forms.

·  Permender R, et al;17 reported Simultaneous estimation of Amlodipine besylate and Lisinopril dehydrate as A.P.I and in tablet dosage forms by modified form of simultaneous equation method using derivative uv spectroscopy.

·  Prasad Rao MM, et al;18 reported RP-HPLC method for simultaneous estimation of Amlodipine besylate and Metaprolol in combined dosage form.

·  Devi R, et al;19 developed new spectrophotometric method for simultaneous determination of Amlodipine besylate and Atorvastatin calcium in tablet dosage forms.

·  Gopal G, et al;20 reported development and validation simultaneous estimation of Amlodipine besylate and Enalapril maleate in combined dosage form.

·  Gowri N, et al;21 developed RP-HPLC method for Simultaneous estimation of Amlodipine besylate and Benazepril .

6.3 OBJECTIVES OF THE STUDY:

Literature survey reveals that no spectrophotometric methods could be found for simultaneous estimation of Amlodipine besylate and Lisinopril in combined dosage forms and no method is available in pharmacopoeias.

In view of the above fact the following attempts are being made to:

Ø  Develop new analytical methods for the simultaneous estimation of Amlodipine besylate and Lisinopril preferably by spectrophotometric methods;

§  Simultaneous equation method (Vierodt’s method).

§  First order derivative method.

§  Area under the curve method.

§  Q-ratio method.

Ø  Develop new chromatographic methods for the simultaneous estimation of Amlodipine besylate and lisinopril by HPLC and HPTLC.

Ø  Validate the proposed methods in accordance with BP, USP and ICH guidelines for the intended analytical applications.

Ø  Apply the proposed methods for the analysis of drugs in their bulk and pharmaceutical dosage form.

7.  Materials and Methods:

7.1 Source of Data:

  1. Internet – National College of Pharmacy, Shimoga.
  2. Kuvempu University Library, Shimoga.
  3. I.I.Sc Library, Banglore.
  4. RGUHS Library, Banglore.

7.2 Method of collection of data:

For the present investigation of the new analytical methods for simultaneous estimation of Amlodipine besylate and. lisinopril, we are in need of Shimadzu 1700 double beam Spectrophotometer, HPLC (Knauer HPLC pump K-501, U.V Detector K-2501), other Chromatographic instruments and volumetric glass apparatus which are available in the lab of Pharmaceutical Analysis Department, National College of Pharmacy, Shimoga.

Journals:

1)  Indian drugs.

2)  IL Farmaco.

3)  Indian journal of pharmaceutical sciences.

4)  Indian journal of analytical chemistry and analyst.

5)  International journal of pharmacy & pharmaceutical sciences.

6)  Journal of Pharmaceutical and Biomedical Analysis.

7)  Journal of Chromatography B: Biomedical Application.

8)  The Open Chemical and Biomedical Methods Journal.

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS ?

------NO ------

7.4 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3 ?

------NOT APPLICABLE------

8. REFERENCES:

  1. Joel GH, Lee EL, Alfred GG. Goodman and Gilman’s the pharmacological basis of therapeutics, 11th ed. Mc Graw Hill, New York, U.S.A; 2001. p. 743,853.
  2. http://en.wikipedia.org/wiki/Amlodipine.
  3. Indian Pharmacopoeia. Indian Pharmacopoeia Commission, Ghaziabad, 2010;2:806,1593.
  4. British Pharmacopoeia. Ph Euro monograph 1590. London, Medicines and Health care products Regulatory Agency (MHRA);2003;1:126.
  5. John HB, John MB Jr. Wilson and Gisvold’s text book of organic medicinal and pharmaceutical chemistry. 11th ed. Lippincott Williams and Wilkins. p. 646.
  6. O’Neil MJ. The Merck index- an encyclopedia of chemicals, drugs and biologicals, 13th ed. New Jersy, Merck and Co., INC; 491,5541.
  7. Sweetman SC. Martindale; the complete drug reference. Pharmaceutical press, 33rd ed. London; 2002;200.
  8. Meyyanathan SN, Muralidharan S, Rajan S, Gopal K, Suresh B. A simple sample preparation with HPLC-UV method for estimation of Amlodipine from plasma: Application to bioequivalence study. The Open Chemical and Biomedical Methods J; 2008;1:22-7.
  9. Yuanyuan M, Feng Q, Xiaohong S, Xiumei L, Famei L. Determination and pharmacokinetic study of Amlodipine in human plasma by ultra performance liquid chromatography-electrospray ionization mass spectroscopy. J of Pharm and Biomed Anal; 2007;43:1540-5.
  10. Rahman N, Manisha S, Nasrul H. Applications of oxidants to the spectrophotometric determination of Amlodipine besylate in pharmaceutical dosage forms. IL FARMACO; 2004;59;913-19.
  11. Rahman N, Nasrul H . Validated spectrophotometric methods for the determination of Amlodipine besylate in drug formulations using 2,3dichloro5,6dicyano1,4 benzoquinone and ascorbic acid. J of pharmaceutical and biomedical analysis; 2003:381-92.
  12. Dhabale PN, Burande KB, Hosmani AH, Gonjari ID, Rakesh SU, Priyanka RP. Development and statistical validation of UV spectrophotometric method for estimation of Amlodipine besylate in tablet dosage form. Arch pharm sci and res; 2009;1(2):158-61.
  13. Divyakanth P, Sharad K, Yogesh CY, Seth AK, Gajanan JD, Ghelani KT. RP-HPLC methods for development and validation of Lisinopril tablets. An Int.J of pharmaceutical sciences; 2011:1000-8.
  14. Basaviah K, Tharpa K, Hiriyanna SG, Vinay KB. Spectrophotometric determination of Lisinopril in pharmaceuticals using Ninhydrin-a modified approach. J of food and drug analysis; 2009;17(2):93-9.
  15. Raza A, Ansari TM, Rehman A. Spectrophotometric determination of Lisinopril in pure and pharmaceutical formulations. J of Chinese chemical society; 2005;52:1055-59
  16. Jamakhandi CM, Chandrasekhar J, Satish Kumar, Santosh Kumar, Sanjay Kumar DS. New fluorimetric method of determination for Lisinopril dosage forms. Int.J of pharma sciences and drug research; 2010;2(3):182-87.
  17. Permender R, Sushila R, Shyama T, Vikash Kumar. Simultaneous estimation of Amlodipine besylate and Lisinopril dehydrate as A.P.I and in tablet dosage forms by modified form of simultaneous equation method using derivative uv spectroscopy. Int. J of PharmaTech research; 2010;2(1):556-62.
  18. Prasada Rao MM, Rahaman SA, Ragjendra PY, Gangi RP. RP-HPLC method for simultaneous estimation of Amlodipine besylate and Metaprolol in combined dosage form. IJPRD; 2010;2(9):69-76.
  19. Devi R, Ramakrishna S. New spectrophotometric methods for simultaneous estimation of Amlodipine besylate and Atorvastatin calcium in tablet dosage form. Int.J Pharmacy and Pharm Sciences; 2010;2(4): 215.
  20. Gopal G, Shailendra S, Swarnlata S. Development and validation simultaneous estimation of Amlodipine besylate and Enalapril maleate in combined dosage form; Trends in Applied Science Research; 2008;3(3):278-84.
  21. Gowri N, Vaidhyalingam V, Shantha A. Simultaneous estimation of Amlodipine besylate and Benazepril from tablet by RP-HPLC. Indian Drugs; 2002;39(10):532-35.

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