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Development of Instrumental Methods for Simultaneous Estimation of Lansoprazole and DomperidoneA Dissertation Submitted to

Pacheri Bari, Dist.-Jhunjhunu

Rajasthan-333515

In partial fulfillment of the requirements for theMaster of PharmacyinPharmaceutical ChemistryUnder the Supervision ofDr. Mandev B. Patel Mr. Subhajit GhoshAsst. Professor Asst. Professor

Submitted ByTaraknath ChatterjeeEnrollment No. 918501375

CERTIFICATE BY THE GUIDEThis is to certify that the dissertation entitled Development of Instrumental Methods for Simultaneous Estimation of Lansoprazole and Domperidone is a bonafide research work done by Mr. Taraknath Chattetrjee in partial fulfillment of the requirements for the degree of Master of Pharmacy in Pharmaceutical Chemistry. Such materials as obtained from other sources have been duly acknowledged in this thesis. This report is now ready for examination.

Date: Dr. Mandev B. Patel Place: Assistant Professor Dept. of Pharmaceutical Chemistry SHIVDAN SINGH INSTITUTE OF TECHNOLOGY & MANAGEMENT

10th Km. STONE, ALIGARH-MATHURA ROAD, ALIGARH (U.P.)

Contact No. : (0522) 257260, 257280, Fax : (05722) 257337

Website:www.seglko.org

CERTIFICATE BY THE GUIDEThis is to certify that the dissertation entitled Development of Instrumental Methods for Simultaneous Estimation of Lansoprazole and Domperidone is a bonafide research work done by Mr. Taraknath Chatterjee under the guidance of Mr. Subhajit Ghosh, Asst. Professor, Department of Pharmaceutical Sciences, SSITM, Aligarh.

Date: Mr. Subhajit GhoshPlace: Asst. Professor Dept. of Pharmaceutical Chemistry SSITM, Aligarh. SHIVDAN SINGH INSTITUTE OF TECHNOLOGY & MANAGEMENT

10th Km. STONE, ALIGARH-MATHURA ROAD, ALIGARH (U.P.)

Contact No. : (0522) 257260, 257280, Fax : (05722) 257337

Website:www.seglko.org

ENDORSEMENT BY THE HOD OF THE INSTITUTIONThis is to certify that the dissertation entitled Development of Instrumental Methods for Simultaneous Estimation of Lansoprazole and Domperidone is a bonafide research work done by Mr. Taraknath Chatterjee under the guidance of Mr. Subhajit Ghosh, Asst. Professor, Department of Pharmaceutical Sciences, SSITM, Aligarh.

Date:

Mr. Md. Hedaytullah

Place:

HOD, Dept. of Pharmacy

SSITM, Aligarh

DECLARATION BY THE RESEARCH SCHOLARI hereby declare that this dissertation entitled Development of Instrumental Methods for Simultaneous Estimation of Lansoprazole and Domperidone is a bonafide and genuine research work carried out by me under the guidance of Mr. Subhajit Ghosh, Asst. Professor, Department of Pharmaceutical Chemistry, S.S.I.T.M,Aligarh and Dr. Mandev B. Patel, Assistant Professor, Dept. of Pharmaceutical Sciences, Singhania University.

Date:

Place: Aligarh (Taraknath Chatterjee)

I would like to take the golden opportunity to express my humble gratitude on the successful completion of my thesis work. Firstly I am very thankful to Mr. Subhajit Ghosh. Asst. Professor, Department of Pharmaceutical Chemistry, SSITM, Aligarh. And Dr. Mandev B. Patel, Asst. Professor, Department of Pharmaceutical Sciences, Singhania University. I am honored to work under his guidance and have his precious guidelines, constant encouragement and support throughout my research work. I am very obliged for the patience with which he guided me at every step of my research work.

My sincere thanks to Mr. Md. Hedaytullah Professor & Head, Dept. of Pharmaceutical Science, SSITM, Aligarh, for his valuable guidelines and timely procurement apparatus and chemical required.I am very grateful to all the teaching and non teaching staff of SSITM, Especially Mr. Yogesh, Mr. Deepak, Mr. Santosh and Librarians whose valuable assistance had helped me a lot in the experiments and literature survey.The discipline, cooperation, and perseverance which I had learned being in SSITM, will be cherished in all the walks of my life.I will not forget to thank my friends Anupam, Kishor, Sayantan and Subha for their love and affection.I would like to remember my juniors, Sandeep, Roop and Santosh for their support through the course and I thank them all for their suggestions, care and friendship.My heartily thanks to my loving family, my mother Mrs. Suchitra Chatterjee, my, father Dr. Biswanath Chatterjee, Especially to my wife Priyanka who has been my strength, my inspiration, and who had always been there, to make my dreams come true. I am deeply indebted to my family for their love and affection.Lastly, I sincerely thank god for all his blessings and all those who had helped me directly or indirectly during my research work.

Date:

Place: C O N T E N T SChapter No. TitlePage No.

1.INTRODUCTION1-35

1.1Introduction to Analytical Chemistry1-3

1.2Steps for Analytical Development3-6

1.3Introduction to Spectroscopy6-8

1.4 Introduction to HPLC8-12

1.5 Analytical Method Validation13-21

1.5.1. Objective of Validation13

1.5.2. Benefits14

1.5.3. Analytical validation characteristics14-21

1.6Multicomponent analysis21-25

1.6.1. Spectrophotometric multicomponent analysis21-22

1.6.2.Various spectrophotometric techniques22-26

1.7 Chemometrics

1.7.1. Application of Chemometrics on spectral data

1.7.2. Statistical parameters to evaluate the efficiency of calibrations mode26-29

27-29

30-30

1.8Drug Profile 31-35

2.OBJECTIVE 36

3.REVIEW OF LITERATURE 38-41

4.METHODOLOGY42-111

Part A

UV Spectrophotometric methods for Simultaneous Estimation Of Domperidone and Lansoprazole.42-92

4.1. Introduction 42-46

4.2. Simultaneous equation method47-55

4.3. First derivative zero crossing method 56-64

4.4. Ratio derivative Spectrophotometric method65-76

4.5. Chemometric method (PLS, PCR and CLS)77-92

Part B

4.6. RP - HPLC Method for Simultaneous Estimation ofDomperidone and Lansoprazole.93-111

5.RESULTS AND DISCUSSION112-114

6.CONCLUSION115

7.SUMMARY116-117

8.BIBLIOGRAPHY118-125

9.ANNEXURE

9.1. List of Tables

9.2. List of Figures126-129

LIST OF TABLESTable No.TitlePage No.

4.1.1Composition of DOMP and LANS in preparation of Binary mixture 46

4.2.1(a)Intra day precision (repeatability)52

4.2.1(b)Inter day precision (intermediate precision)52

4.2.2Application of standard addition technique to the analysis of DOMP and LANS in Lanspro-D Capsules 53

4.2.3Reproducibility of the method by three different analysts54

4.2.4LOD and LOQ of DOMP and LANS54

4.2.5Analysis of commercial formulation55

4.3.1Optimized method parameters59

4.3.2(a)Intra day precision (repeatability)61

4.3.2(b)Inter day precision (intermediate precision)61

4.3.3Application of standard addition technique to the analysis of DOMP and LANS in Lanspro-D Capsules62

4.3.4LOD and LOQ of DOMP and LANS62

4.3.5Reproducibility of the method by three different analysts63

4.3.6Analysis of commercial formulation64

4.4.1(a)Analytical data of the calibration graphs for the determination of DOMP and LANS by the ratio spectra derivative method 67

4.4.1(b)Application of the proposed procedure for the simultaneous determination of the two drugs in laboratory prepared mixtures69

4.4.2Calibration data (Linearity data) for standard dilutions of DOMP and LANS73

4.4.3Intra day precision for determination of DOMP and LANS 74

4.4.4Inter day precision for determination of DOMP and LANS74

4.4.5Recovery study from synthetic mixture75

4.4.6LOD and LOQ75

4.4.7Analysis of commercial formulation76

4.5.1Composition of the concentration (calibration) set 80

4.5.2Statistical parameters of chemometric methods in calibration step of Zero-order spectra85

4.5.3Statistical parameters of chemometric methods in prediction step of Zero-order spectra90

4.5.4Application of standard addition technique to the analysis of DOMP and LANS in Lanspro-D Capsules90

4.5.5Recovery results in prediction from Zero- order spectra for DOMP and LANS in synthetic mixtures by proposed chemometric techniques91

4.5.6Results obtained for the pharmaceutical samples by using chemometric calibrations91

4.5.7Precision study results of prepared binary mixture92

4.6.1Composition of the concentrations and recoveries results100

4.6.2Linearity data for DOMP and LANS 101

4.6.3Characteristic parameters of calibration equation for the proposed HPLC method for simultaneous determination of DOMP and LANS. 103

4.6.4Precision study results of prepared binary mixture105

4.6.5Application of standard addition technique to the analysis of DOMP and LANS in Lanspro-D Capsules. 106

4.6.6Ruggedness report of DOMP and LANS107

4.6.7Robustness of chromatographic method108

4.6.8Results of system suitability parame