6.
7.
8. / ENCLOSURE-I
BRIEF RESUME OF THE INTENDED WORK:
6.1 GENERAL DISCUSSION :
Esomeprazole magnesium is a highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and Zollinger-ellison syndrome. The drug inhibits the H (+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in the proton pump of gastric parietal cells.
Structural Formula :

Nomenclature : Di-(S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)
methyl]-sulfinyl]-1H-benzimidazole magnesium trihydrate
Molecular formula : C17H19N3O3S.Mg.3H2O.
Molecular weight : 767.2 g/mol.
Characteristics : White or Slightly coloredcrystallinepowder.
Category : Anti-Ulcer Agents, Anti histamine, Proton pump inhibitors.
Solubility : Slightly soluble in water, Soluble in methanol.
6.2NEED 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. These determinationsrequire highly sophisticated instruments and methods like HPLC, HPTLC, GasChromatography and Spectrophotometer etc.
Extensive literature survey reveals that several analytical methods havebeen reported for the estimation of Esomeprazole magnesium in pharmaceutical dosage form which includes Spectrophotometricmethods [3],[4],[5]., HPLC[6]and RP-HPLC[7],[8].
Hence there is a need for the development of newer, simple, sensitive, rapid, accurateand reproducible analytical methods for the routine estimation of Esomeprazole magnesium in bulk and pharmaceutical dosage form.
6.3 REVIEW OF LITERATURE :
  1. Nafisur Rahman,et al [3]., studied on Spectrophotometric Determination of Esomeprazole Magnesium in Commercial Tablets Using 5-Sulfosalicylic Acid and N-Bromosuccinimide.
  2. Lakshmana prabu S, et al[4]., studied on Simultaneous Estimation of Esomeprazole and Domperidone by UV Spectrophotometric Method.
  3. Patil Shamkant S, et al[5]., studied on Development and Statistical Validation of Spectrophotometric Method for Estimation of Esomeprazole in Tablet Dosage Form.
  4. Armagan onal, et al[6]., studied onHigh Performance Liquid Chromatographic method was developed and validated for the analysis of Esomeprazole magnesium trihydrate (ES) in tablets.
  5. Roosewelt C,et al[7]., studied on Simultaneous Method Development and Validation of Esomeprazole and Domperidone in Pure and Pharmaceutical Dosage Forms By RR-HPLC.
  6. Patel BH, et al[8]., studied onDetermination of Pantoprazole, Rabeprazole, Esomeprazole, Domperidone and Itopride in Pharmaceutical Products by Reversed Phase Liquid Chromatography using single mobile phase.
  7. Ia Hultman, et al[9]., studied on Determination of Esomeprazole and its two main metabolites in human, rat and dog plasma by Liquid Chromatography with Tandem Mass Spectrometry .
6.4OBJECTIVES OF THE STUDY:
The study of Esomeprazole magnesiummakes an attempt to establish sensitive and accurate methods for the estimation of Esomeprazole magnesium in pure and pharmaceutical dosage form.
In view of the need for a suitable method for routine analysis ofEsomeprazole magnesium in formulations, attempts are being made to develop simple, precise and accurate analytical methods for estimation ofEsomeprazole magnesium 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 Esomeprazole magnesium in pure and dosage form.
  • To validate the newly developed methods in accordance with the analytical parameters mentioned in the ICH guidelines.[10],[11]
  • To apply the newly developed, validated analytical methods for quantitative estimation of Esomeprazole magnesiumin bulk and pharmaceutical dosage forms.
ENCLOSURE-II
MATERIALS AND METHODS:
MATERIALS:
  • All the chemical and reagents for the development of new analytical method to estimate Esomeprazole magnesium will be of analytical grade.
  • The pure sample of Esomeprazole magnesium for the research work will be produced from Everest Organics Ltd, Hyderabad.
  • 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 Esomeprzole magnesium in bulk and pharmaceutical dosage form.
METHODS:
  • Based on solubility of Esomeprazole magnesium Spectrophotometric methods like Derivative spectroscopyand differencespectroscopy methodwill be developed.
  • Chromatographic methods like RP-HPLCandHPTLCwill be developed by using different solvent system and flow rate.
  • Colorimetric methods will be developed depending upon the chemical nature (functional group, chromophore) of Esomeprazole magnesium.
  • Other New method like Atomic Absorption Spectroscopy can be planed as Esomeprazole magnesium contains magnesium ion.
7.1.Source of Data:
  1. Library, Bharathi College of Pharmacy.
  2. E-library, Bharathi College of Pharmacy.
  3. Library, RGUHS,Bangalore.
  4. Library IISC, Bangalore.
  5. Library IICT, Hyderabad.
  6. Internet.
7.2. Method of Collection of Data:
DATA COLLLECTED FROM:
Considering the chemical structure and reactivity of Esomeprazole magnesium with various reagents to produce the chromogens of analytical importance the various methods for the quantitative estimation are planned.
JOURNALS:
  1. Journal of Chinese Chemical Society.
  2. Indian Journal of Pharmaceutical Sciences.
  3. Asian Journal Research Chemicals.
  4. Journal of Food and Drug Analysis.
  5. Asian Journal of Chemistry.
  6. Journal Chromatographia.
  7. Journal of Chromatography B.
.
RELATED LINKS:





7.3DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONSTO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
NOT APPLICABLE
7.4HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
NOT APPLICABLE.
ENCLOSURE-III
REFERENCES:
  1. Nafisur R, Zehra B , Syed N H. Spectrophotometric Determination of Esomeprazole magnesium in Commercial Tablets Using 5-Sulfosalicylic Acid and N-Bromosuccinimide.J Chinese Chem Soc 2008;55(3):557-566.
  2. Lakshmana PS ,Shirwaiker A, kumar DC, Joseph A , Kumar R .Simultaneous estimation of Esomeprazole and Domperidone by UV Spectrophotometric Method.Indian J Pharm Sci 2008;77(1);128-131.
  3. Patil SS, Dhabale PN, Kuchekar BS. Development and statistical validation of Spectrophotometric Method for Estimation of Esomeprazole in Tablet Dosage Form; Asian J Research Chem 2009;2(2);154-156.
  4. Armagan O, Aysel O.High Performance Liquid Chromatographic method was developed and validated for the analysis of Esomeprazole magnesium trihydrate (ES) in tablets. J Food Drug Anal 2005; 14(1);12-18.
  5. RooseweltC,MageshRA,RavisudarA. Simultaneous method development and validation of Esomeprazole and Domperidone in Pure and Pharmaceutical Dosage Forms By RR-HPLC. Asian J chem 2007; 19(7);1.
  6. Patel BH, Suhagia BN,Patel MM ,Patel JR,.Determination of Pantoprazole, Rabeprazole, EsomeprazoleDomperidone and Itopride in Pharmaceutical Products by Reversed Phase Liquid Chromatography using single mobile phase.J Chromatographia2007;65(11-12);743-748.
  7. Hultman I, Stenhoff H , Liljeblad M . Determination of Esomeprazole and its two main metabolites in human, rat and dog plasma by liquid chromatography with Tandem Mass Spectrometry. J chromatogr B 2007;848(2);317-322.
  8. ICH, Q2A Text on Validation of analytical procedures, Oct, 1994.
  9. ICH, Q3B Validation of analytical procedures: methodology, Nov, 1996.