6. / ENCLOSURE-I
BRIEF RESUME OF THE INTENDED WORK
6.1 GENERAL DISCUSSION:
Rosuvastatin calcium [1] is a synthetic, single enantiomer formulated and new member of a class of cholesterol-lowering drugs commonly known as “statins”. Although, dihydroxy heptenoic acid side chain is characteristic of the statin class, but one particular feature of the Rosuvastatin calcium molecule is a polar methane sulphonamide group that confers a relatively low lipophilicity, which make Rosuvastatin calciumrelatively hydrophilic and hepatoselective.Rosuvastatin calcium is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis.Rosuvastatin is orally administered as calcium salt and is mainly used to treat dyslipidemia, hyperlipidemia, hypercholesterolemia and to prevent cardiovascular disease including atherosclerosis.
Structure formula :

Nomenclature : (E)-(3R,5S)-7-{4-(4-fluorophenyl)-6-isopropyl-2-methyl(methylsulpho-
nylamino)]pyrimidin-5-yl}-3,5-dihydroxyhepten-6-oicacid calcium.
Molecular formula : (C22H27FN3O6S) 2Ca.
Molecular weight : 1001.14 g / mol.
Characteristics : White amorphous powder.
Category :Lipid lowering agent.
Solubility : Sparingly soluble in water and methanol and slightly soluble in
ethanol.
6.2 NEED FOR THE STUDY:
Analytical methods are required to characterize drug substances and drug products composition during all phases of pharmaceutical development.Development of methods to achieve the final goal of ensuring the quality of drug substances and drug products must be implemented in conjunction with an understanding of the chemical behavior and physicochemical properties of the drug substance. This determination requires highly sophisticated instruments and methods like HPLC, HPTLC, Gas Chromatography and Spectrophotometer etc.
Extensive literature survey reveals that several analytical methods have been reported for the estimation of Rosuvastatin calcium in pharmaceutical dosage form which includes Spectrophotometric methods[2][3][4], Stability indicating method[5], HPTLC[5] and RP-HPLC.[6][7][8]
Apart from above no other spectroscopic and chromatographic methods like Derivative spectroscopy, Area Under Curve, HPLC and HPTLC methods were reported for this compound. Hence there is a need for the development of newer, simple, sensitive, rapid, accurateand reproducible analytical methods for the routine estimation of Rosuvastatin calcium in bulk and pharmaceutical dosage form.
6.3 REVIEW OF LITERATURE:
  1. Dannana GS,et al[2]., Studied on Extractive spectrophotometric methods for the determination of Rosuvastatin calcium in pure form and in pharmaceutical formulations by using Safranin O and Methylene blue.
  2. Gupta A, et al[3]., Studied on Simple UV spectrophotometric determination of Rosuvastatin calcium in pure form and in pharmaceutical formulations.
  3. Singh RM, et al[4]., Studied on spectrophotometric estimation of Rosuvastatin calcium in tablet formulation.
  4. Hasumati AR, et al[5]., Studied on Development and validation of two chromatographic stability-indicating methods for determination of Rosuvastatin in pure form and pharmaceutical preparation.
  5. Singh RM, et al[6]., Studied on Determination of Rosuvastatin calcium in pharmaceutical dosage form by RP-HPLC method.
  1. Singh SS, et al[7]., Studied on Estimation of Rosuvastatin in human plasma by HPLC Tandem Mass Spectroscopic method and its application to bioequivalence study.
  2. Thammera RK, et al[8]., Studied on Determination of Rosuvastatin in rat plasma by HPLC and its application to pharmacokinetic studies.
  3. Chaudhari BG, et al[9]., Studied on Determination of Simvastatin, Pravastatin sodium and Rosuvastatin calcium in tablet dosage forms by HPTLC.
6.4OBJECTIVES OF THE STUDY:
In view of the need for a suitable method for routine analysis ofRosuvastatin calcium in formulations, attempts are being made to develop simple, precise and accurate analytical methods for estimation ofRosuvastatin calcium and extend it for their determination in formulation.
In the proposed work attempts shall be made to:
  • To establish sensitive and accurate methods for the quantitative estimation of Rosuvastatin calcium in pure and dosage form.
  • To validate the newly developed methods in accordance with the analytical parameters for quantitative estimation of Rosuvastatin calcium in bulk and pharmaceutical dosage forms mentioned in the ICH guidelines.[10][11]

7. / ENCLOSURE-II
7.1 MATERIALS AND METHODS:
MATERIALS:
  • All the chemical and reagents for the development of new analytical method to estimate Rosuvastatin calcium will be of analytical grade.
  • The pure sample of Rosuvastatin calcium for the research work will be produced from Zydus-Cadila Pharmaceutical Ltd, Ahmedabad.
  • Spectral measurementwill be carried out using Shimadzu UV-VIS Spectrophotometer 1800.
  • Shimadzu HPLC model containing LC-20AT (VP series) pump, variable wavelength programmable UV/VIS detector SPD-20A (VP series) will be used for HPLC method.
  • Camag Linomat V sample applicator and Camag TLC Scanner 3 equipped with Win-CAT software will be employed for the development and validation of new HPTLC method for the estimation of Rosuvastatin calcium in bulk and pharmaceutical dosage form.
METHODS:
  • Based on solubility of Rosuvastatin calcium the spectrophotometric methods like Derivative spectroscopy, Difference spectroscopy and Area UnderCurve method will be developed.[12]
  • Chromatographic methods like RP-HPLC by using internal standard or by stress degration method [13] and HPTLC [14] by using economic solvent system and different flow rate will be developed.
  • Colorimetric methods will be developed depending upon the chemical nature (functional group, chromophore) of Rosuvastatin calcium.
  • Other new method like Atomic Absorption Spectroscopy will be planed as Rosuvastatin contains calcium ion.
7.2 SOURCE OF DATA:
  1. IISC Library, Bangalore.
  2. Bharathi College of Pharmacy Library, Bharathinagara.
  3. RGUHS Library, Bangalore.
  4. E-Library, Bharathi College of Pharmacy.
7.3 METHOD OF COLLECTION OF DATA:
DATA COLLECTED FROM
JOURNALS:
  1. E-Journal of Chemistry.
  2. India Journal of Pharmaceutical Science.
  3. Indian Drugs.
  4. Biomedical Chromatography.
  5. International Journal of Chemtech Research.
  6. Journal of Pharmaceutical And Biomedical Analysis.
  7. Journal of Chromatographic Science.
RELATED LINKS:






7.4DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
NOT APPLICABLLE.
7.5 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOURINSTITUTION IN CASE OF 7.4?
NOT APPLICABLE
8. / ENCLOSURE-III
REFERANCES:
1.Indian Pharmacopoeia.Ghaziabad: The Indian Pharmacopoeia Commission; 2007 vol 3 p. 1676-1678.
2.Dannana GS, Marothu VK. Extractive Spectrophotometric methods for the determination of Rosuvastatin calcium in pure form and in pharmaceutical formulations by using safranin O and methylene blue. E J Chem 2007;4(1):46-49.
3.Gupta A,Mishra P, Shah K. Simple UV Spectrophotometric determination of Rosuvastatin calcium in pure form and in pharmaceutical formulations. E J Chem 2009;6(1):89-92.
4.Singh RM, Ansari TA, Jamil S, Kumar Y, Mathur SC, Singh GN.Spectrophotometric estimation of Rosuvastatin calcium in tablet formulation. Indian Drugs 2005;42(4):244-245.
5.Hasumati AR, Rajput SJ,Dave JB, Patel CN. Development and validation of two chromatographic stability-indicating methods for determination of Rosuvastatin in pure form and pharmaceutical preparation. Int J ChemTech Res 2009;1(3):677-689.
6.Singh RM, Jami S, Ansari TA, Mathur SC, Nivoria CS, Pandey MK et al. Determination of Rosuvastatin calcium in pharmaceutical dosage form by RP-HPLC method. Indian Drugs 2005;42(2):98-101.
7.Singh SS, Sharma K, Patel H, Jain M, Shah H, Gupta Set al. Estimation of Rosuvastatin in human plasma by HPLC Tandem Mass Spectroscopic method and its application to bioequivalence study. J Braz Chem Soc 2005;16(5):944-950.
8.Thammera RK, Shitut NR, Pasikanti KK, Menon VCA, Venkata VPK, Mullangi Ret al.Determination of Rosuvastatin in rat plasma by HPLC and its application to pharmacokinetic studies.Biomed Chromatogr 2006;20(9):881-887.
9.Chaudhari BG, PatelNM, Shah PB. Determination of Simvastatin, Pravastatin sodium and Rosuvastatin calcium in tablet dosage forms by HPTLC. Indian J Pharm Sci2007;69(1):130-132.
10.ICH, Q2A Text on validation of analytical procedures, Oct, 1994.
11.ICH, Q3B Validation of analytical procedures: methodology, Nov, 1996.
12.Beckett AH, Stenlake JB. Pharmaceutical Chemistry. 4th ed. Part two. New Delhi: CBS; 1997. p. 302-305.
13.Snyder LR, Kirkland JJ, Glajch JL. Practical HPLC method development. 2nd ed. New York: Wiley Inter Science; 1997. p. 1-50.
14.Sethi PD. HPTLC: Quantitative analysis of pharmaceutical formulations. 1st ed. New Delhi: CBS Publisher; 1996. p. 53-57.