Development of Conductometric Method for Quantification of Metformin HCl in Bulk and Pharmaceuticals

doi:10.21203/rs.3.rs-2214144/v1

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Research Article

Development of Conductometric Method for Quantification of Metformin HCl in Bulk and Pharmaceuticals

https://doi.org/10.21203/rs.3.rs-2214144/v1

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Purpose

The main objectives of proposed research work is to develop and validate novel cost effective conductometric method for quantification of Metformin HCl in bulk and its marketed pharmaceuticals.

Methods

The proposed conductometric method makes the use Millipore water as solvent system for the analysis. The method was developed by preparing various concentration of analyte in water and measuring the electrical conductance. In order to measure the electrical conductivity of analyte solution ELICO CM 183EC-TDS analyser version 2.3 was utilized. The developed method was validated in order to standardize its performance as per current regulatory recommendations.

Results

Metformin HCl displayed the linearity between the concentration ranges of 50 to 250 µg/mL with r² value of 0.9999. The % relative standard deviation observed at each validation parameters was well within the acceptance with less than 2% RSD. The recovery values were observed between 99 to 100%.

Conclusion

The newly established and authenticated conductometric tool was found to be realistic for quantification of Metformin HCl in its marketed tablet pharmaceuticals.

Drug Discovery, Design, & Development

Metformin HCl

Conductometric Method

Diabetes Mellitus

Validation

Pharmaceuticals

The assay development of drugs and their formulation is very much essential and important in the pharmaceutical drug manufacturing industries. The quality assessment and evaluation of pharmaceutical formulations during product development stage in pharmaceutical industry is crucial step. The analytical valuation is the critical approach in quality control of pharmaceutical formulations. The poor analytical assessment may lead to generation of inaccurate values and assessment result that may be risky to the drug and product formulation stage. The analytical assessment of drugs can be done by using many modern instruments and investigative techniques which can be used to control the quality of medicines or drugs from natural origin. The analytical techniques are classified into various categories like chromatographic techniques, optical methods or spectral techniques, physical methods or thermo analytical methods, electrochemical techniques, biological and microbiological methods, titrimetric methods, radioactive methods and miscellaneous methods (Pathuri 2013).

The electrochemical methods are the group of analytical methods which measures the electrochemical properties or characteristics of drug substances. The electrochemical methods includes conductometric, potentiometric and amperometric analysis. The conductometric examination is a research laboratory apparatus used for the quantitative inspection and mainly used to know the amount of a given analyte in a mixture. It comprises the measurement of electrical conductivity of the solution. It can be well-known that the electrical conductivity of an electrolytic solution is reliant on the quantity of free ions in the solution and the charge conforming to each of these ions and it also be contingent on concentration of analyte (Siddiqui 2013). Some recompenses of the conductometric titration procedure are like this development is very useful in the measurement of very dilute solutions and weak acids, this kind of investigation is appropriate for solutions that are coloured or turbid, and they also has numerous applications in oxidation and reduction titrations, acid and base titrations, titrations involving the formation of precipitation, and complexometric titrations (Sankar 2010).

Metformin HCl is well known orally bioavailable antidiabetic chemical belongs to the biguanides moiety and excellently employed for the treatment and management of diabetes mellitus type-II. It mainly displays its mechanism of action by decreasing the glucose secretion. It reported to decreases the level of cholesterol and hence the weight loss in few cases (EI 2011) It is also recommended in the management and treatment of “polycystic ovary syndrome” (Radosh 2009). It is available in market and promoted in many of its single as well as in its combined dosage form with other antidiabetic medications. In the year 1922 it was synthesized by reaction of dimethylamine hydrochloride and 2-cyanoguanine in the existence of temperature (Werner 1921) Metformin HCl found to possess and reports few adverse effects like lactic acidosis and few issues related to gastro intestinal tract. It is recommended and contraindicated to use this drug in the patients with diseases of kidney, liver, lung and heart disorders (Sonnett 2009). Metformin HCl chemically known as N, N-dimethylimido dicarbonimidic diamide with molecular formula C₄H₁₁N₅ and molecular weight of about 129.164 gm/mol. The drug is freely soluble in water and also it’s sensitive to light and degrades when heated emitting nitric oxide (Suryawanshi 2022). It is available as white to off-white crystalline powder with pKa value 12.4. The chemical arrangement of Metformin HCl is accessible in Fig. 1.

We have reviewed the various reports through literature on the analytical techniques for quality control of Metformin HCl in its bulk and pharmaceutical preparations. We observed that it was analyzed by few spectroscopic, chromatographic, and electrochemical methods. The reported method found to possess some limitations like use of costly instruments, hazardous chemicals, utilization of organic solvents in more amount, use of costly reagents, more time consuming processes, critical steps in extraction, complicated tools in instrument handling, extraction steps are multiple which leads to more time consuming methods. Most of the published chromatographic techniques have limitations as they have complex solvent system composition, more retention factor. (Gul 2016; Suryawanshi 2019; Argun 2016; Williams 2016; Werner 1921; Younk 2012; and Rios 2013).

Conductometric Titration and Quantification of Metformin HCl

There are literatures available for quantification of Metformin HCl using conductometric titrations. The conductometric titration method was simulated and experimented for Metformin HCl. In this method Metformin HCl was estimated by using titration against silver nitrate. The titration mainly involves the reaction between Cl of metformin with silver nitrate. The end point of method was analyzed by using conductometric, potentiometric and visual techniques. In this tool the hypothetical conductance value of the Metformin HCl were designed when well-known amount of titrant are added, using the limit conductivity records for each of the ions existing in the reports. In another reported method the conductometric titration of Metformin HCl in pharmaceutical preparation was assessed using the reagents like silver nitrate. The technique was based on the chemical reaction between the chloride of Metformin HCl and Ag(I) ions, giving the precipitate as AgCl (Valdivia 2019 and Sarteri 2009).

We observed that the reported conductometric methods are based on titrations and in addition they suggested the use of reagents to react with Metformin HCl. As the titrimetric methods are considered to be a time consuming with use of extra and costly reagents like silver nitrate. This indicates the limitations and disadvantages of published reports. In order to overcome and reduce the one or two limitations and disadvantages of reported and published conductometric titration methods for quantification of Metformin HCl there is strong need for development and validation of simple, cost effective, new, and accurate conductometric process for assessment of Metformin HCl in bulk and pharmaceuticals.

The key intentions of planned investigation are to develop and augment a simple, low cost, rapid, rugged, sensitive, robust, reliable, accurate, and cost effective electrochemical (conductometric) method for quantification of Metformin HCl in marketed pharmaceuticals and compare its effectiveness and applicability over the reported and published literatures on conductometric titrations.

The general methodology followed in proposed research is presenetd in Fig. 2. we have selecetd Metformin HCl is oral anti-diabetic agent which is mainly avaialble as tablet pharmaceutical form and many formulations are availble in market. In order to assess the formulations literature has reported few spectroscopic, chromatographic and electrochemical metods. The reporetd electrochemical methods are usually based on potentiometric and conductometric titrations. These electrochemical analysis observed for its own limitationa nd disadvatnges. Hence a novel principle has been applied in order to quantify Metformin HCl where we have preparted various concentartion ranging between 50 to 250 µg/mL and subjecetd to measure the electrical conductance of each concentartion. After measuring the conductance it was observed that as the concentration of analyte in given solution increases the electrical conductnace also increases in linear way. In further investigation we conducted validation in order to confirm the performace of method by evaluatining various parameters like, specificity, selectivity, linearity, range, interday precision, intraday precision, quantification and detection limits, ruggedness, reproducibility, and accuracy as per current regulatory requirements. Further the research has been explored to analyse the accuracy and performance of method to quantify the marketed pharmaceutical preparation containing Metformin HCl.

Apparatus and Instruments

In the current research work we have used electronic analytical weighing balance of SARTORIUS in order to weigh the Metformin HCl bulk drug and tablets, An Ultrasonic bath Sonicator (Ultrasonic cleaner) was used for the purpose of sonication and solubility enhancement, in order to measure the electrical conductance of analyte solution ELICO CM 183EC-TDS analyser version 2.3 was used.

Reagents and chemicals

The Millipore water was obtained from direct-Q UV water purification system from Department of Pharmacognosy, KLE College of Pharmacy, Belagavi.

Process Development

The process was established using an electrical conductivity meter using Millipore water as a cost effective and easily available solvent. A number of concentrations of Metformin HCL were prepared in Millipore water and electrical conductance was noted. Diverse concentrations of Metformin HCl were detected to display changed values of electrical conductivity. The electrical conductivity was observed to be increasing as the concentration increases in linear order. In direction to test the appropriateness of the proposed method, the marketable tablet preparation of Metformin HCL was studied quantitatively. An electrical conductivity meter “ELICO CM 183EC-TDS analyser version 2.3” was used for investigation and its instrumentation is given in Fig. 3 (Yadav 2021).

Preparation of Primary Stock Solution of Metformin HCl

50 mg of Metformin HCl was precisely balanced and transported into 50 mL calibrated volumetric flask and volume was made up to the mark using Millipore water as diluent produce 1000µg/mL (Suryawanshi 2020).

Preparation of Working Standard Solution of Metformin HCl

In order to prepare working standard solutions different volumes of primary stock solution were pipetted out and transferred into separate 50 mL volumetric flasks and volume were made up to the mark using Millipore water to produce 50 to 250 µg/mL of Metformin HCl. (Pancham 2020 and Uday 2021).

Sample Preparation and Extraction Procedure

Twenty tablets of Metformin HCl (500mg label statement) were weighed and powdered. A portion corresponding to 500mg was assessed and added to a 100 mL volumetric flask and volume was made up to 100 mL with Millipore water and sonicated for 20 minutes and the solution was strained by Whatman filter paper. From the above stock solution dilution was done to obtain 100µg/mL concentration. This solution was tested for calculating its percentage purity (Bossunia 2017 and Murugesan 2022).

Validation of Proposed Conductometric Method

International conference on harmonization (ICH) Guidelines were followed in order to validate the proposed new conductometric method in terms of precision, linearity and range, specificity and selectivity, limit of quantification (LOQ), limit of detection (LOD), ruggedness, and accuracy etc (Chandran 2007).

Specificity and Selectivity

The specificity of the process developed was calculated by computing the conductance of Millipore water. In order to prove the specificity of method the standard concentration of Metformin HCL (100µg/mL) was prepared and conductance was measured.

Linearity and Range

The linearity method is useful in order to evaluate and quantify different concentration ranging from lower to higher value of drug concentrations. It was evaluated by preparing different concentrations and measuring the electrical conductivity. The standard concentration containing 50–250µg/mL of Metformin HCL was prepared and electrical conductivity of each were measured. The calibration standard was constructed by scheming the amount of analyte versus electrical conductance (µS) and statistical calculations were done to produce linearity and range data.

Detection and Quantification Limits of Analyte: The detection limit of analyte is the lowermost quantity of analyte which can be sensed but not precisely measured and it was resolute by using statistical formula: LOD = 3.3\(\frac{\sigma }{S}\).

The quantification limit is the quantity of analyte which can be sensed and quantitatively resolute with exact precision and it was intended by using the formula: LOQ = 10\(\frac{\sigma }{S}\).

Where\(\sigma\) = standard deviance and S = slope of the standardisation typical curve.

Precision

The precision was approved out in terms of intraday and interday by performance of analysis in triplicate solutions at lower, middle and higher concentration levels. The conductance of three replicate concentration of Metformin HCl at three different quantity was measured, and % Relative Standard Deviation (RSD) standards of each for its obtained conductance were measured. The intraday precision was evaluated on same day at three different time intervals and Interday precision was determined by performing the analysis on three different days.

Ruggedness

the ruggedness of proposed process was conceded out by altering the specialist to check the reproducibility of technique. It was measured by examining the triplicate solutions at lower, middle and higher concentration levels and measuring the electrical conductivity. The % RSD values were calculated and observed for its accuracy.

Accuracy

Accuracy was established by using recovery experiments, by the estimation of % mean recovery of sample at three diverse levels like 150%, 100%, and 50%. At every level, three determinations were approved out and % mean recovery was designed. The standard addition method was used to know the accuracy of proposed analytical technique.

Quality Assessment and Quantification of Metformin HCl using Validated Conductometric Assay Method

Twenty tablets of Metformin HCl (500mg label statement) were collected and powdered. An amount corresponding to 500mg was balanced and added to a 100mL volumetric flask and the final volume was made up to 100 ml using Millipore water and sonicated for 20 minutes and the solution was strained by Whatman sieve paper. From the above stock solution dilution was done to obtain 100µg/mL concentration. This solution was tested for calculating its percentage purity. In order to extract the accurate amount of analyte, small amount of methanol was used and trial studies were performed.

The proposed method was found to be definite as the conductance of Millipore water was found to be 1.18µS and that of the 100µg/mL of Metformin HCl was found to be 60.66 µS and hence the outcomes of the examination were establish to be selective and specific. Metformin HCl analyte showed a linear association amongst electrical conductance (µS) versus its concentration level of 50 to 250 µg/mL. The calculation of the straight line for Metformin HCl was found to be r² value 0.9999. The evaluation and statistical linearity and range data was showed in Table 1. The standard calibration curve was attained by plotting against concentration against the measured electrical conductance of standard solution and presented in Fig. 4. The detection and quantification limit values obtained for Metformin HCl were 3.12µg/mL and 9.47µg/mL respectively. Both results are in the acceptance range. The precision study values indicates the preciseness of proposed method on same and different days. The precision values obtained at lower, middle and higher concentration level were observed to be less than 2% RSD limit. The outcomes of data were presented in Tables 2 and Table 3. The ruggedness of proposed method was performed by different analyst and the % RSD values were calculated for measured conductance which was found to be less than 2%. The data of ruggedness was recorded in Table 4. The recovery experiments was performed at three different level mainly at 150%, 100%, and 50%. The individual recovery and % mean recovery were establish between the ranges of 99 to 100% which indicates that the accuracy of proposed method. The % mean recovery values and data was recorded and presented in Table 5.

Table 1

Linearity Data of Metformin HCl by Conductometric Method
Concentration µg/ml	Set-1 Electrical conductivity (µS)	Set-2 Electrical conductivity (µS)	Set-3 Electrical conductivity (µS)	Mean Electrical conductivity (µS)
50 µg/ml	31.10	30.33	30.20	30.54
100 µg/ml	61.66	61.50	60.90	61.35
150 µg/ml	90.80	91.10	90.70	90.87
200 µg/ml	120.10	120.12	121.12	120.45
250 µg/ml	150.15	149.95	150.10	150.07
r²	0.9998	0.9998	0.9999	0.9999

Table 2

Intraday Precision Data of Metformin HCl
Concentration	Time	Conductance (µS)(x̄)	SD	%RSD
50 µg/mL	Morning Afternoon Evening	30.62 30.74 30.86	0.51 0.36 0.23	1.65 1.18 0.75
150 µg/mL	Morning Afternoon Evening	91.03 90.83 91.02	0.07 0.06 0.18	0.08 0.07 0.20
250 µg/mL	Morning Afternoon Evening	150.78 150.56 150.77	0.59 0.47 0.40	0.39 0.31 0.27
x̄ = Mean conductance of three replicates.

Table 3

Interday Precision Results of Metformin HCl
Concentration	Time	Conductance (µS)(x̄)	SD	%RSD
50 µg/mL	Day-1	31.18	1.12	3.58
	Day-2	30.94	0.16	0.51
	Day-3	30.82	0.17	0.55
150 µg/mL	Day-1	90.76	0.05	0.06
	Day-2	91.02	0.19	0.21
	Day-3	90.97	0.08	0.08
250 µg/mL	Day-1	150.480	0.33	0.22
	Day-2	151.040	0.12	0.08
	Day-3	150.790	0.60	0.40
x̄ = Mean of three replicates of conductance

Table 4

Ruggedness Data of Metformin HCl
Replicates	Concentration	Change in Analyst-1	Concentration	Change in Analyst-2
1	50 µg/mL	31.11	150 µg/mL	91.78
2	50 µg/mL	31.80	150 µg/mL	93.80
3	50 µg/mL	30.90	150 µg/mL	92.70
4	50 µg/mL	30.66	150 µg/mL	90.90
5	50 µg/mL	31.11	150 µg/mL	91.05
6	50 µg/mL	30.80	150 µg/mL	90.95
Mean		31.063	Mean	91.863
SD		0.401	SD	1.173
%RSD		1.292	%RSD	1.277

Table 5

Accuracy Data of Metformin HCl
Sl. No.	Level	Replicate	% Recovery	Mean % Recovery	%SD
1	50%	1	99.90	99.90	0.05
		2	99.95
		3	99.85
2	100%	1	100.10	100.04	0.06
		2	100.05
		3	99.98
3	150%	1	99.86	99.98	0.15
		2	100.15
		3	99.94

The assay was conceded out by using Metformin HCl tablets (make claim 500 mg) were taken and the equivalent weight was measured and diluted to obtain 100 µg/ml concentration. The assay results were obtained in an acceptable range of 99.78%

The proposed method was found to be use of Millipore water as solvent for analysis and also it do not suggest the any extra solvents and costly reagents for performing the dilutions or the purpose of derivatization. After preparing various concentrations of analyte in the Millipore water, they were subjected to the measurement of conductance. This allow easy performance of analysis with very lower cost and less time consumption. Which is very much essential and needful in the pharmaceutical industries manufacturing Metformin HCl. The proposed method were subjected to quantify the marketed pharmaceuticals containing Metformin HCl to see and evaluate the applicability and reproducibility of proposed novel electrical conductometric method. The detailed comparison of proposed research method along with reported or published literature methods was presented in Table 6.

Table 6

Comparison of Proposed Conductometric Method with Literature Methods
Parameters	Reported/Published Methods	Proposed Research Work Method
Development	Conductometric titrimetric methods	Conductometric methods
Solvents and Reagents	Diluents and Reagents-silver nitrate and Ag(I)	Millipore Water
Performance of Method	Titrations are involved	Only simple dilutions and measuring the conductance of analyte solution
Cost with respect to use of solvents and reagents	Approximately 3000 to 4000/- for each 25 gm.	0% (As we have used Millipore water)
Time of Analysis	More time is required as it involves the use of titrations	Less time is required as it do not suggest the use of titrations

The quality valuation of medications and its medicinal formulations is very significant and vital during product expansion stage in medicinal industry. Metformin HCl is an orally given antidiabetic drug product belongs chemically in biguanides category and efficiently employed for managing the diabetes mellitus type 2 in many patients. There are literatures available for quantification of Metformin HCl using conductometric titrations. The reported conductometric methods are based on titrations and in addition they suggested the use of reagents to react with Metformin HCl. As the titrimetric methods are considered to be a time consuming with use of extra and costly reagents like silver nitrate. In order to overcome these limitations and disadvantages of published reports, we have proposed new conductometric method using Millipore water as solvent. The newly developed and validated method was found to be of new, cost effective, simple, and accurate for conductometric estimation of Metformin HCl in bulk and pharmaceuticals.

Finally we have compared the method with existed literature and we concluded that the proposed method was found to be use of Millipore water as solvent for analysis and also it do not suggest the any extra solvents and costly reagents for performing the dilutions or the purpose of derivatization. After preparing various concentrations of analyte in the Millipore water, they were subjected to the measurement of conductance. This allow easy performance of analysis with very lower cost and less time consumption. Which is very much essential and needful in the pharmaceutical industries manufacturing Metformin HCl.

A simple, precise, rapid, low-cost conductometric method was developed and validated using electrical conductometer ELICO CM 183EC-TDS analyser version 2.3. Further the research has been explored to analyse the accuracy and performance of method to quantify the marketed pharmaceutical preparation containing metformin HCl. The proposed conductometric tool was found to be simple, precise and accurate and can be successfully used for marketed pharmaceutical preparations containing Metformin HCl.

Acknowledgement:

The authors are very thankful to Principal Dr. S. S. Jalalpure and Vice Principal Dr. M. B. Patil for their support and guidance. Authors are also thankful to the Department of Pharmaceutical Chemistry KLE College of pharmacy, Belagavi.

Conflict of interests: The authors declare that they have no conflict of interest.

Statement of Human and Animal Rights: This article does not contain any studies with human and animal subjects performed by any of the authors.

HCl

Hydrochloride

%RSD

Percentage Residual Standard Deviation

% SD

Percentage Standard Deviation

Pathuri R, Muthukumaran M, Krishnamoorthy B, Nishat A (2013) A review on analytical method development and validation of pharmaceutical technology. Current Pharma Research. 3(2):855.
Siddiqui MR et al.,(2013) Analytical techniques in pharmaceutical analysis: A review. Arabian Journal of Chemistry 1–13.
Bhoop BS (2014) Quality by Design (QbD) for holistic pharma excellence and regulatory compliance. Pharm times 46(8):26–33.
El Messaoudi S, Rongen GA, de Boer RA, Riksen NP 2011 The cardioprotective effects of metformin. Curr Opin Lipidol 22(6):445–53.
Radosh L (2009) Drug treatments for polycystic ovary syndrome. Am Fam Physician 79(8):671–6.
Werner E, Bell J (1921) The preparation of methylguanidine and of dimethyl guanidine by the interaction of di cyano diamide and methylammonium and dimethylammonium chlorides respectively. J Chem Soc Trans 121:1790–5.
Sonnett TE, Levien TL, Neumiller JJ, Gates BJ, Setter SM (2009) Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus. ClinTher 31(2):245–59.
Suryawanshi SS, Palled MS (2022) Box-Behnken Design Assisted Optimization and Standardization of Chromatographic Methodology for Quality Assessment of Metformin: Analytical Quality by Design Avenue. Indian J of Pharmaceutical Education and Research 56(2s):s152-s162.
Gul W (2016) Metformin: methods of analysis and itsrole in lowering the risk of cancer. J Bio equiv 08(6):254–9
Suryawanshi D, Jha DK, Shinde U, Amin PD (2019) Development and validation of a stability-indicating RP-HPLC method of cholecalciferol in bulk and pharmaceutical formulations: analytical quality by design approach. J App Pharm Sci 9(6):21–32.
Argun M, Üzüm K, Sönmez MF, Özyurt A, Karabulut D, Soyersarica Z, Çilenk KT, Unalmis S et al., (2016) Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats. The Anatolian Journal of Cardiology 1;16(4):234.
Williams T, Mortada R, Porter S (2016) Diagnosis and treatment of polycystic ovary syndrome. American family physician 94(2):106–13.
Werner E, Bell J (1921) The preparation of methylguanidine and of dimethyl guanidine by the interaction of di cyano diamide and methylammonium and dimethylammonium chlorides respectively. J Chem Soc Trans 121:1790–5.
Younk LM, Davis SN (2012) Evaluation of colesevelam hydrochloride for the treatment of type 2 diabetes. Expert opinion on drug metabolism and toxicology 8(4):515–25.
Rizos CV, Elisaf MS (2013) Metformin and cancer. European Journal of Pharmacology 705(1–3):96–108.
Valdivia AE, Montaño-Osorio C, Vargas-Rodríguez YM (2019) Conductometric Titration of Metformin Hydrochloride: Simulation and Experimentation. J. Chem 13:105–11.
Sartori ER, Suarez WT, Fatibello-Filho O (2009) Conductometric determination of metformin hydrochloride in pharmaceutical formulations using silver nitrate as titrant. Química Nova 32:1947–50.
Yadav RK, Maste MM, Suryawanshi SS, Shastri U (2021) Journal of Applied Pharmaceutical Science 11(11):82–6.
Suryawanshi SS, Kavalapure R, Palled MS, Alegaon SG (2020) Development and Validation of UV-Spectrophotometric Method for Determination of Ciprofloxacin and Curcumin in Bulk Powder. Int J Pharm Sci and Res 11:1161–6.
Pancham YP, Girish B, Suryawanshi SS (2020) UV-Spectrophotometric method for quantification of ascorbic acid in bulk powder. J. Pharm. Innov 9:05–8.
Uday TC, Shivabasappa PM, Sanjay SS, Maruti MS (2021) Development and Validation of Stability Indicating UV-Spectrophotometric Method for the Simultaneous Estimation of Telmisartan and Metformin Hydrochloride in Bulk Drugs. Indian J of Pharmaceutical Education and Research 55(2):590–7.
Bossunia MTI, Urmi KF, Shaha CK (2017) Quality-by-design approach to stability indicating RP-HPLC analytical method developmentfor estimation of Canagliflozin API and its validation. Pharm Methods 8(2):92–101. doi: 10.5530/phm.2017.8.15.
Murugesan A, Annapurna M (2022) Simple Quantified and Validated Stability Indicating Stress Degradation Studies of Oral Anti-Diabetic Agent Dapagliflozin by Rp-Hplc Method. Int J App Pharm 14(1):231–7.
Chandran S, Singh RS 2007 Comparison of various international guidelines for analytical method validation. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 1;62(1):4–14.

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Development of Conductometric Method for Quantification of Metformin HCl in Bulk and Pharmaceuticals

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Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Conductometric Titration and Quantification of Metformin HCl

Materials And Methods

Preparation of Primary Stock Solution of Metformin HCl

Preparation of Working Standard Solution of Metformin HCl

Sample Preparation and Extraction Procedure

Results

Discussion

Conclusion

Declarations

Abbreviations

References

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