A SYNOPSIS OF THE THESIS ENTITLED

Transcription

1 A SYNOPSIS OF THE THESIS ENTITLED DEVELOPMENT AND VALIDATION OF CHROMATOGRAPHIC AND SPECTROSCOPIC METHODS FOR ESTIMATION OF SOME ANTIHYPERTENSIVE AGENTS AND THEIR COMBINED DOSAGE FORMS Submitted To Gujarat Technological University, Ahmedabad For Partial fulfillment of the Degree of Doctor of Philosophy In Faculty of Pharmacy (Pharmaceutical Sciences) SUBMITTED BY (M.Pharm) Registration No 9164 Enrollment No RESEARCH GUIDE Dr. Nehal Shah (M. PHARM., Ph. D.) Professor and Principal, Indubhai Patel College of pharmacy and research Centre, Dharmaj, Anand, Gujarat.

2 Sr. No. CONTENTS Title Page No. 1 Introduction 1 2 Aim of Present work 2 3 Experimental work 3 4 Summary 8 5 Conclusion 9 6 References 10 7 Publications 14

3 INTRODUCTION [1-3] : Hypertension is an abnormal increase in diastolic and/or systolic pressure. 1 billion people worldwide and is a leading cause of mortality. About 20% of people of world are hypertensive, and one-third of are not even aware they are hypertensive. Therefore, this disease is sometimes called the "silent killer. A condition present when blood flows through the blood vessels with a force greater than normal. Hypertension can strain the heart, damage blood vessels, and increase the risk of heart attack, stroke and kidney problems and cause death. The newer Antihypertensive drugs and their combinations are approved by FDA. These newer drugs and their combinations are not official in any pharmacopeias and take more time to include in pharmacopoeia. In order to overcome analytical difficulties for newer antihypertensive drugs, it is required to develop and validate newer analytical methods for simultaneous estimation drugs in pharmaceutical formulations. Elevated blood pressure develops gradually over many years usually without a specific identifiable cause. However, possible medical causes, such as medications, kidney disease, adrenal problems or thyroid problems, must first be excluded. High blood pressure that develops over time without a specific cause is considered benign or essential hypertension. Blood pressure also tends to increase as a person ages. A primary risk factor for prehypertension is being overweight. Other risk factors include a sedentary lifestyle, eating high sodium foods, smoking and excessive alcohol intake. Blood pressure levels appear to be familial, but there is no clear genetic pattern. 1

4 2. AIM OF PRESENT WORK: To develop and validate of analytical methods for simultaneous estimation of anti-hypertensive drugs in pharmaceutical dosage form. There are numbers of newer antihypertensive drugs and their formulations are approved by FDA which is either new molecule or partial modification of existing molecule. These newer drugs and their combinations are not official in any pharmacopeias and are take more time to include in pharmacopeias. Because of continuous and longer use of these drugs individually newer side effects, toxicity, resistances are observed. So present investigation was undertaken with a view to develop and validate new analytical methods for simultaneous estimation of 1. Olmesartan medoxomil (20 mg) and Indapamide (1.5 mg) tablets 2. Olmesartan medoxomil (20 mg) and Chlorthalidone (12.5 mg) tablets 3. Metoprolol succinate (50 mg) and Chlorthalidone (12.5 mg) tablets 4. Nebivolol Hydrochloride (5 mg) and Chlorthalidone (12.5 mg) tablets 5. Rosuvastatin calcium (10 mg) and Hydrochlorthiazide (12.5 mg) tablets OBJECTIVES To develop RP-HPLC methods for simultaneous estimation of Olmesartan medoxomil and Indapamide, Olmesartan medoxomil and Chlorthalidone, Nebivolol HCl and Chlorthalidone, Rosuvastatin calcium and Hydrochlorthiazide, Metoprolol succinate and Chlorthalidone in combination drug products. To develop UV or HPTLC methods (wherever UV method is not feasible) for simultaneous estimation of Olmesartan medoxomil and Indapamide, Olmesartan medoxomil and Chlorthalidone, Nebivolol HCl and Chlorthalidone, Rosuvastatin calcium and Hydrochlorthiazide, Metoprolol succinate and Chlorthalidone in combination drug products. All developed methods to be validated for specificity, linearity, accuracy, repeatability (precision), ruggedness, limit of detection and limit of quantification, robustness and system suitability. To perform statistical comparison of developed methods. 2

5 3. Experimental work HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD Simultaneous estimation of Olmesartan medoxomil and Indapamide from bulk and commercial products using a validated reverse phase high Performance liquid chromatographic technique [4]. A simple, rapid, accurate, sensitive, precise and economical reverse phase high performance liquid chromatographic (RP-HPLC) method is developed and validated (as per ICH guidelines) for simultaneous separation and quantification of two anti-hypertensive drugs Olmesartan Medoxomil and Indapamide. The separation of both the drugs was achieved on ACE C 18 AR column (250 x 4.6 mm, 5 µ m) column using a mobile phase of Sodium Perchlorate and triethylamine buffer solution (at ph 3): Acetonitrile (60:40 v/v). The flow rate was 1 ml/min and detection was done at 280 nm. The retention time for Indapamide was 5.3 min and for Olmesartan Medoxomil was 6.8 min. Olmesartan medoxomil and Indapamide showed a linear response in the concentration range of µ g/ml and µ g/ml, respectively. The correlation co-efficient (' r ' value) for Olmesartan Medoxomil and Indapamide was and , respectively. The percentage recoveries obtained for Olmesartan medoxomil and Indapamide ranges from 99.3% to 100% and 99% to 100.7%, respectively. The results of analysis have been validated as per ICH guidelines. The extremely low flow rate, simple mobile phase composition makes this method cost effective, rapid and non-tedious and can also be successfully employed for simultaneous estimation of both drugs in commercial products. Simultaneous estimation of Olmesartan medoxomil and Chlorthalidone from bulk and commercial products using a validated reverse phase high performance liquid chromatographic technique [5-6]. A simple, rapid, accurate, precise and economical reverse phase high performance liquid chromatographic method is developed and validated (as per ICH guidelines) for simultaneous separation and quantification of two anti-hypertensive drugs, Chlorthalidone and Olmesartan medoxomil. The separation of both the drugs was achieved on Inertsil ODS 3V C18 column (250 x 4.6 mm id, 5 µm particle size) column using a mobile phase of sodium dihydrogen phosphate buffer solution (at ph 3): acetonitrile (48:52 v/v). The flow rate was 1 ml/min and detection was done at 270 nm. The retention time for Chlorthalidone was 3.65 min and Olmesartan medoxomil was 6.23 min. Chlorthalidone and Olmesartan medoxomil showed a linear response in the 3

6 concentration range of µ g/ml and µ g/ml, respectively. The correlation coefficients for Chlorthalidone and Olmesartan medoxomil were and , respectively. The percentage recoveries obtained for Chlorthalidone and Olmesartan medoxomil ranges from 99.5% to 100.1% and 99.1% to 100.4%, respectively. Simultaneous estimation of Chlorthalidone and Nebivolol hydrochloride from bulk and commercial products using a validated reverse phase high performance liquid chromatographic technique [7-10]. A simple, rapid, accurate, precise and economical reverse phase high performance liquid chromatographic method is developed and validated (as per ICH guidelines) for simultaneous separation and quantification of two anti-hypertensive drugs, Chlorthalidone and Nebivolol hydrochloride. The separation of both the drugs was achieved on zorbax eclipse XDB C8 column (250 x 4.6 mm id, 5 µm particle size) column using a mobile phase of Potassium dihydrogen phosphate and triethylamine buffer solution (at ph 3): acetonitrile (65:35 v/v). The flow rate was 1 ml/min and detection was done at 280 nm. Results: The retention time for chlorthalidone was 4.36 min and Nebivolol hydrochloride was 9.68 min. Chlorthalidone and Nebivolol hydrochloride showed a linear response in the concentration range of µg/ml and µ g/ml respectively. The correlation co-efficients for Chlorthalidone and Nebivolol hydrochloride were and respectively. The percentage recoveries obtained for Chlorthalidone and Nebivolol hydrochloride ranges from 99.4% to 100.5% and 99.4% to 99.8% respectively. Validation results indicated that method shows satisfactory results. Simultaneous estimation of Metoprolol succinate and Chlorthalidone in pharmaceutical solid dosage form by using a developed and validated reverse phase high performance liquid chromatographic technique [11-13]. The separation of both the drugs was achieved on Inertsil ODS 3 column (100 x 4.6 mm, 5 µm) column using a mobile phase of diammonium hydrogen phosphate buffer solution (at ph 5.5): Methanol (70:30 v/v). The flow rate was 1.0 ml/min and detection was done at 254 nm. The retention time for Metoprolol succinate was 6.91 min and Chlorthalidone was 9.94 min. Metoprolol succinate and Chlorthalidone showed a linear response in the concentration range of µ g/ml and µ g/ml respectively. The correlation co-efficients for Metoprolol succinate and chlorthalidone were Metoprolol succinate and Chlorthalidone and , 4

7 respectively. The percentage recoveries obtained for ranges from 98.9% to 100.6% and 98.5% to 99.2% respectively. The results of analysis have been validated as per ICH guidelines. Validation results indicated that method shows satisfactory linearity, accuracy, precision and ruggedness. Simultaneous estimation of Rosuvastatin calcium and Hydrochlorthiazide from bulk and commercial products using a validated reverse phase high performance liquid chromatographic technique [14-15]. A simple, rapid, accurate, precise and economical reverse phase high performance liquid chromatographic ( RP-HPLC) method is developed and validated (as per ICH guidelines) for simultaneous separation and quantification of two cardiovascular drugs, viz., Rosuvastatin calcium and Hydrochlorthiazide. The separation of both the drugs was achieved on ACE C18 AR column (250 x 4.6 mm, 5 µm) column using a mobile phase of sodium perchlorate buffer solution (at ph 3.0): Acetonitrile (60:40 v/v). The flow rate was 1 ml/min and detection was done at 280 nm. Results: The retention time for Hydrochlorthiazide was 3.9 min and for Rosuvastatin calcium was 10.3 min. Rosuvastatin calcium and Hydrochlorthiazide showed a linear response in the concentration range of 5-30 µ g/ml and µ g/ml respectively. The correlation co-efficients for Rosuvastatin calcium and Hydrochlorthiazide were and respectively. The percentage recoveries obtained for Rosuvastatin calcium and Hydrochlorthiazide ranges from 99.3% to 100.4% and 99.2% to 100.4% respectively. UV spectrophotometric method Simultaneous estimation of Olmesartan medoxomil and Indapamide by standard addition UV Spectrophotometric method in their combined dosage forms [16-17] A simple, accurate, precise, reproducible and economical UV spectroscopic method for simultaneous estimation of Olmesartan medoxomil and Indapamide in marketed formulation is developed and validated as per ICH guidelines. Method employs solving of simultaneous equations based on the measurement of absorbance at two wavelengths 256 nm and 240 nm which are the λmax values of Olmesartan medoxomil and Indapamide in methanol.a predetermined concentration of Indapamide (6 μg/ml) was added to standard and sample solution to obtain concentration of Indapamide in range of UV estimation and to decrease effect of low dose. This predetermined concentration is deducted from final results to get exact concentration 5

8 of drug.the linearity of method was investigated in range of 5-25 µ g/ml for Olmesartan medoxomil and 5-25 µ g/ml for Indapamide respectively. The results of analysis have been validated for linearity, accuracy and precision, ruggedness, solution stability, LOD and LOQ of the proposed method. This method can be successfully employed for simultaneous estimation of all drugs in commercial products. Simultaneous UV spectrophotometric method for simultaneous estimation of Olmesartan medoxomil and Chlorthalidone in their combined dosage forms [18-19]. A simple, accurate, precise, reproducible and economical UV spectroscopic method for simultaneous estimation of Chlorthalidone and Olmesartan medoxomil in marketed formulation is developed. Method employs solving of simultaneous equations based on the measurement of absorbance at two wavelengths 220 nm and 254 nm which are the λmax values of Chlorthalidone and Olmesartan medoxomil in methanol. The linearity of method was investigated in range of 5-25 µ g/ml for Chlorthalidone and 5-25 µ g/ml for Olmesartan medoxomil respectively. The results of analyses have been validated for linearity, accuracy and precision, ruggedness, LOD and LOQ of the proposed method. This method can be successfully employed for simultaneous estimation of all drugs in commercial products. Simultaneous UV spectrophotometric method for simultaneous estimation of Chlorthalidone and Nebivolol hydrochloride in their combined dosage forms [20]. A simple, accurate, precise, reproducible and economical UV spectroscopic method for simultaneous estimation of Chlorthalidone and Nebivolol Hydrochloride in marketed formulation is developed. Method employs solving of simultaneous equations based on the measurement of absorbance at two wavelengths 226 nm and 282 nm which are the λmax values of Chlorthalidone and Nebivolol hydrochloride in methanol. The linearity of method was investigated in range of 5-25 µ g/ml for Chlorthalidone and 5-25 µ g/ml for Nebivolol hydrochloride respectively. This method can be successfully employed for simultaneous estimation of all drugs in commercial products. 6

9 Simultaneous UV spectrophotometric method for simultaneous estimation of Rosuvastatin calcium and Hydrochlorthiazide in their combined dosage forms [21-24]. A simple, accurate, precise, reproducible and economical UV spectroscopic method for simultaneous estimation of Rosuvastatin calcium and Hydrochlorthiazide in marketed formulation is developed and validated (as per ICH guidelines). Method employs solving of simultaneous equations based on the measurement of absorbance at two wavelengths 243 nm and 270 nm which are the λmax values of Rosuvastatin calcium and Hydrochlorthiazide in methanol. The linearity of method was investigated in range of 5-15 µg/ml for Rosuvastatin calcium and µ g/ml for Hydrochlorthiazide respectively. The results of analyses have been validated statistically for linearity, accuracy and precision, ruggedness, LOD and LOQ of the proposed method. This method can be successfully employed for simultaneous estimation of all drugs in commercial products. HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHIC METHOD [25-27] Simultaneous estimation of Metoprolol succinate and Chlorthalidone in pharmaceutical solid dosage form by using a developed and validated high performance thin layer chromatographic technique This work represents development and validation (as per ICH guidelines) of novel, accurate, precise, rugged, robust and reproducible high performance thin-layer chromatographic technique for the simultaneous estimation of Metoprolol succinate and Chlorthalidone from marketed formulation. High performance thin-layer chromatography was performed using HPTLC aluminium plates precoated silica gel plate 60 F 254 as stationary phase. The solvent system consisted of toluene: ethyl acetate: methanol: triethylamine (6: 1: 1: 0.6 v/v/v/v) as the mobile phase for the separation of Metoprolol succinate and Chlorthalidone at 230 nm. The method was found to be linear in the range of ng spot 1 for Metoprolol succinate and ng spot 1 for Chlorthalidone. R f value for Metoprolol succinate and Chlorthalidone is 0.53 and 0.24 respectively. The relative standard deviation (% RSD) values of the precision study were <2% which indicated that the developed method was precise; recovery was found to be 99.9% % for Metoprolol succinate and 99.9% % Chlorthalidone respectively. The extremely simple mobile phase composition makes this method cost effective, rapid and nontedious. 7

10 4. SUMMARY RP-HPLC methods for simultaneous estimation of Olmesartan medoxomil and Indapamide, Olmesartan medoxomil and Chlorthalidone, Nebivolol HCl and Chlorthalidone, Rosuvastatin calcium and Hydrochlorthiazide, Metoprolol succinate and Chlorthalidone in combination drug productswere developed. UV spectroscopic methods for simultaneous estimation of Olmesartan medoxomil and Indapamide, Olmesartan medoxomil and Chlorthalidone, Nebivolol HCl and Chlorthalidone, Rosuvastatin calcium and Hydrochlorthiazide, in combination drug products were developed. HPTLC method for simultaneous estimation of Metoprolol succinate and Chlorthalidone in combination drug products was developed. All developed methods to be validated for specificity, linearity, accuracy, repeatability (precision), ruggedness, limit of detection and limit of quantification, robustness and system suitability. Statistical comparison of methods is performed. 8

11 5. CONCLUSION Validated simultaneous RPHPLC method have been developed and successfully applied for estimation of Olmesartan medoxomil and Indapamide, Olmesartan medoxomil and Chlorthalidone, Nebivolol HCl and Chlorthalidone, Rosuvastatin calcium and Hydrochlorthiazide, Metoprolol succinate and Chlorthalidone in their combination drug products on HPLC with PDA detector and isocratic elution. Optimization of buffer solution ph, ratio of mobile phase concentration and use of proper organic phase in mobile phase to improve peak shape was a critical part of method. The shorter retention time cuts down cost of experiment. Good resolution between all three drugs was best key part of developed method. Specificity and selectivity of method was an added as set to method for routine analysis of drug samples in Analytical development laboratories and Quality control laboratories. Validated simultaneous UV spectrophotometric methods have been developed and successfully applied for simultaneous estimation of Olmesartan medoxomil and Indapamide, Olmesartan medoxomil and Chlorthalidone, Nebivolol HCl and Chlorthalidone, Rosuvastatin calcium and Hydrochlorthiazide in their combination drug products using UV Spectrophotometer. Low interference in UV method gives precise and reproducible results. Validated HPTLC analytical method has been developed for simultaneous estimation of Metoprolol succinate and Chlorthalidone in their combination drug products. The developed method is simple, precise specific and selective for simultaneous drug estimation. Data analysis proves that method is reproducible and accurate. The advantages of method are low cost of reagents, rapid analysis by method and excellent peak shapes. Developed HPTLC methods meet system suitability criteria, peak integrity and proper peak resolution. A low detection and quantitation limit of method proves high sensitivity of method. An acceptable % CV values confirms that method is precision of method. 9

12 6. REFERENCES 1) Whitworth JA (2003), World Health Organization, International Society of Hypertension Writing Group World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension, Journal of Hypertension, 21(11), pp , ISSN No: ) Guidelines Committee (2003), European Society of Hypertension: European Society of Cardiology guidelines for the management of arterial hypertension, The Journal of Hypertension, 21(6), pp , ISSN No: ) Mire, David E, Silfani TN, Pugsley MK (2005), A Review of the Structural and Functional Features of Olmesartan Medoxomil, An Angiotensin Receptor Blocker, Journal of Cardiovascular Pharmacology, 46 (5), pp ,ISSN No: ) Ganduri MR, Lanka RA (2010) New RP-HPLC method for the determination of olmesartan medoxomil in tablet dosage form, Eurasian Journal of Analytical Chemistry, 5(2), pp , ISSN No: ) Verma PK, Kamboj VK, Ranjan S (2010), Spectrophotometric Estimation of Olmesartan Medoxomil in Tablet Dosage Form with Stability Studies, International. Journal of chem Tech Research, 2(2), pp , ISSN No: ) Barot D, Pradhan PK, Patel G, Shah S, Parmar HP, Dey S, Upadhyay UM (2014), Simultaneous UV spectrophotometric estimation of Olmesartan medoxomil and chlorthalidone in tablet dosage Form, The Pharma Innovation Journal, 3(10), pp 76-80, ISSN No: ) Saunders E, Smith WB, DeSalvo KB (2007), The efficacy and tolerability of nebivolol in hypertensive African American patients, TheJournal of Clinical Hypertension, 9(11), pp , ISSN No: ) Meyyanathan S, Rajan S, Murlidharan S, Birajdar A, Suresh B (2008), A Validated RP- HPLC Method for Simultaneous Estimation of Nebivolol and Hydrochlorothiazide in Tablets, Indian Journal of Pharmaceutical Sciences, 70(5), pp , ISSN No: X. 10

13 9) Modiya J S, Pandya CB, Channabasavaraj KP (2010), Simultaneous Estimation of Nebivolol HCl and Valsartan in Bulk and Capsule Dosage Form by Simultaneous Equation Method. International Journal of Chem Tech Research, 2(3), pp , ISSN No: ) Mishra P, Shah K, Gupta A (2009), Spectrophotometric methods for simultaneous estimation of Nebivolol HCl and Amlodipine besylate in tablets, International journal of pharmacy and pharmaceutical sciences, 1, pp 55-61, ISSN No: ) Patel S, Patel D (2013), Simultaneous Determination Of Metoprolol Succinate And Chlorthalidone By UV Spectrophotometric Method, Pharmagene, 1(3), pp 39-43,ISSN No: ) Desai D, Vashi N, Dalvadi H, Desai S, Hinge M (2016), HPTLC Method Development and Validation of Cilnidipine and Metoprolol Succinate in Combined Dosage Form, Pharmaceutical Methods, 7(1), pp 28-34, ISSN No (print): ) Nivedita G. et al (2012), Simultaneous Estimation of Atenolol and Chlorthalidone as Bulk and in Tablet Dosage form by UV-Spectrophotometry, IOSR Journal of Pharmacy and Biological Sciences, 1(4), pp 20-23, ISSN No: ) Tian D, Tian X, Taian T, Wang Z, Mo F (2008), Simultaneous Determination of Valsartan and Hydrochlorothiazide in Tablets by RP-HPLC, Indian Journal of Pharmaceutical Sciences, 70(3), pp , ISSN No: X. 15) Gomes PF, Garcia PL, Alves JMP, Singh AK, Kedor-Hackmann ERM, Maria IRMS (2009), Development and Validation of Stability-Indicating HPLC Methods for Quantitative Determination of Pravastatin, Fluvastatin, Atorvastatin, and Rosuvastatin in Pharmaceuticals, Analytical Letters., 42(12), pp ) Patel DD, Patel MM (2012), Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Pharmaceutical Dosage Form by UV Spectroscopy, International Journal of Research in Pharmaceutical and Biomedical Sciences, 3(2), pp , ISSN No:

14 17) Vora BN, Parmar RR, Nayak PP, Shah DA (2012), Development and validation of the simultaneous UV spectrophotometric method for estimation of metoprolol succinate and olmesartan medoxomil in the tablet dosage form, Pharmaceutical Methods, 3(1), pp 44 47, ISSN No (print): , ISSN (online): X. 18) Padmane SP, Jain ND, Ittadwar AM, Walde S (2014), A Derivative UV-Spectrophotometric Method for the Simultaneous Determination of Metoprolol Succinate and Chlorthalidone in Combined Dose Tablet Formulation, International Journal of Analytical and Bioanalytical Chemistry, 4(1), pp 33-41, ISSN No: ) Barot D, Pradhan PK, Patel G, Shah S, Parmar HP, Dey S, Upadhyay UM (2014), Simultaneous UV spectrophotometric estimation of Olmesartan medoxomil and chlorthalidone in tablet dosage Form, The Pharma Innovation Journal, 3(10), pp 76-80, ISSN No: ) Nivedita G. et al (2012), Simultaneous Estimation of Atenolol and Chlorthalidone as Bulk and in Tablet Dosage form by UV-Spectrophotometry, IOSR Journal of Pharmacy and Biological Sciences, 1(4), pp 20-23, ISSN No: ) Gupta A, Mishra P, Shah K (2005), UV Spectrophotometric Determination of Rosuvastatin Calcium in Pure Form and in Pharmaceutical Formulations, E-journal of chemistry, 6(1), pp 89 92, ISSN No: ) Karunakaran A, Subhash V, Chinthala R, Muthuvijayan J (2011),Simultaneous Estimation of Rosuvastatin Calcium and Fenofibrate in Bulk and in Tablet Dosage Form by UV- Spectrophotometry and RP-HPLC, Stamford Journal of Pharmaceutical Sciences, 4(1), pp 58-63, ISSN No: ) Hemke AT, Bhure MV, Chouhan KS, Gupta KR and Wadodkar SG (2010), UV Spectrophotometric Determination of Hydrochlorothiazide and Olmesartan Medoxomil in Pharmaceutical Formulation, E-Journal of Chemistry, 7(4), pp , ISSN No: ) ICH (1996), Proceedings of the International Conference on Harmonisation of Technical Requirement of Registration of Pharmaceuticals for Human Use (ICH Harmonised Tripartite Guidelines). Validation of Analytical Procedures: Methodology, Q2B; Geneva, Switzerland. 12

15 25) Patil VP, Kulkarni VS, Devdhe SJ, Kawde RV, Kale SH (2012), Simultaneous HPTLC Analysis of Hydrochlorthiazide and Metoprolol Succinate in Tablet and Bulk Dosage Form, World Research Journal of Organic Chemistry, 1(1), pp 1-5, ISSN No: , ISSN (online): ) Kunjir VV, Jadhav SB, Purkar AJ, Chaudhari PD (2012), Validated HPTLC Method for Simultaneous Determination of Olmesartan Medoximil and Metoprolol Succinate in Tablet Dosage Form, Indian Drugs, 49(10), pp 13-17, ISSN No (Print): X. 27) Ginoya CG, Thakkar DV (2013), Development and Validation of HPTLC Method for Simultaneous Determination of Metoprolol Succinate and Atorvastatin Calcium in Pharmaceutical dosage form, International Research Journal of Pharmacy, 4(2), pp , ISSN No:

16 7. PUBLICATIONS 1. Avani Sheth, Chhagan N Patel, Badmanaban Ramlingam, Nehal Shah. Simultaneous estimation of Metoprolol succinate and Chlorthalidone in pharmaceutical solid dosage form by using a developed and validated reverse phase high performance liquid Chromatographic technique. Scholars' Research Journal, 2012, 2 (1 and 2), 17-21, ISSN No: Avani Doshi, K. N. Patel, R. Badmanaban, Naman Doshi, Nehal Shah. Simultaneous estimation of Olmesartan medoxomil and Indapamide from bulk and commercial products using a Validated Reverse Phase High Performance Liquid Chromatographic technique.chronicles of young scientist, 2013, 4(1), 69-73, ISSN No: Avani Sheth, C N Patel, Nehal Shah.Simultaneous Estimation of Chlorthalidone and Olmesartan Medoxomil from Bulk and Commercial Products using a Validated Reverse Phase High Performance Liquid Chromatographic Technique. Inventi Rapid: Pharm Analysis & Quality Assurance, 2013, (3), 01-05,ISSN No: Avani Sheth, C N Patel, Nehal Shah.Simultaneous Estimation of Chlorthalidone and Nebivolol Hydrochloride from Bulk and Commercial Products using a Validated Reverse Phase High Performance LiquidChromatographic Technique.Inventi Rapid: Pharm Analysis & Quality Assurance, 2013, (3), 01-05, ISSN No: Avani Sheth, KN Patel, Badmanaban Ramlingam, Nehal Shah. Simultaneous estimation of Rosuvastatin calcium and Hydrochlorthiazide from bulk and commercial products using a validated reverse phase high performance liquid chromatographic technique. Scholars' Research Journal, (1 and 2), 07-12, ISSN No: Avani sheth, Nehal Shah. Simultaneous UV spectrophotometric method for simultaneous estimation of Olmesartan medoxomil and Chlorthalidone in their combined dosage forms. Pharma Science Monitor An International Journal Of Pharmaceutical Sciences, 2016,7(3), , ISSN No: Sheth A H, Patel C N, Shah N J, UV Spectrophotometric method for simultaneous estimation of Chlorthalidone and Nebivolol hydrochloride in their combined dosage forms. Indian drugs, 2016, 53(11), 38-45, ISSN No: X. 8. Sheth Avani H, C N Patel, Nehal Shah, Simultaneous Estimation of Metoprolol Succinate and Chlorthalidone in Pharmaceutical Solid Dosage Form by usinga Developed and Validated High Performance Thin Layer Chromatographic Technique,Inventi Rapid: Pharm Analysis & Quality Assurance,2017,3, pp 1-9, ISSN No: Avani Sheth, C N Patel, Nehal Shah, Ragin shah. Simultaneous estimation of Olmesartan medoxomil and Indapamide by standard addition UV Spectrophotometric method in their combined dosage forms, Indian drugs, ISSN No: X. LIST OF ACCEPTED ARTICLES 10. Avani Sheth, C N Patel, Nehal Shah, Simultaneous UV spectrophotometric method for simultaneous estimation of Rosuvastatin calcium and Hydrochlorthiazide in their combined dosage forms. Indian drugs, (Acceptation date: 31/01/2017). 14