spectrophotometric estimation of metformin in bulk and in its dosage form
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The document describes the development and validation of a UV spectrophotometric method for the estimation of metformin in bulk and tablet dosage forms. Key aspects include determining the absorption maximum of 646 nm for metformin and developing a linear calibration curve within the concentration range of 8-16 μg/ml. The method was validated based on parameters such as accuracy, precision, LOD, LOQ and recovery, demonstrating the method is simple, accurate, precise and can be used to analyze metformin in pharmaceutical formulations.
spectrophotometric estimation of metformin in bulk and in its dosage form
- 1. Spectrophotometric Method Development For The Estimation of Metformin in its Bulk and Tablet Dosage Form R .SAIKIRAN GOUD IV year B.PHARMACY CMR COLLEGE OF PHARMACY
- 2. CONTENTS Abstract Introduction Review of Literature Drug Profile Need for Study Aim & Objective Plan of Work Materials & Methods Results & Discussion Conclusion Bibliography
- 3. ABSTRACT Metformin is a biguanide antihyperglycemic agent used for treating non-insulin dependent diabetes mellitus (NIDDM). . The present work is designed to develop a new validated, simple, rapid, efficient, reliable and economic UV spectrophotometric method for the estimation of metformin from pharmaceutical dosage forms. The absorption maxima was measured at 646 nm and is linear over concentration range 8-16µg/ml. The limits of detection and quantification were calculated to be 0.0218 µg/ml& 0.066 µg/ml respectively, percentage drug recovery is 99.2%. Key words: NIDDM , Metformin, biguanide, antihyperglycemic,.
- 4. INTRODUCTION Pharmaceutical Analysis Pharmaceutical analysis is a branch of analytical chemistry that involves a series of process for identification, determination, quantification and purification of a substance, separation of the components of a solution or mixture, or determination of structure of chemical compounds. There are main two types of chemical analysis. 1. Qualitative (identification) 2. Quantitative (estimation) UV VISIBLE SPECTROSCOPY Principle : Beer-Lambert law Beer’s Law :intensity of incident radiation decreases exponentially with the increase in the concentration of the absorbing medium I=I0e-kc
- 5. Lambert’s law Rate of decrease in the intensity of the incident radiation(I) with the thickness of the medium (t) is directly proportional to the intensity of the incident light. dI/dt= kI I/I0 =e-kct A=εct INSTRUMENTATION OF UV
- 6. INSTRUMENTATION Radiation sources (UV) Filter or Monochromator Sample cells Detector METHOD DEVELOPMENT OF UV SPECTROSCOPY 1.Selection of Equipment 2.Equipment Validation 3.Nature Of Sample 4.Selection of solvent 5.Selection of wavelength 6.Sample Handling and measurement OPTIMIZATION OF UV-VISIBLE SPECTROSCOPY • Wavelength • Solvent • Concentration • pH • Temperature
- 7. Method validation Specificity Accuracy Precision Detection of Limit Quantitation Limit Linearity Range Robustness
- 8. Review of Literature Development and Validation of Analytical Method for Determination of Metformin Hydrochloride in Bulk and Tablet Dosage Form by Using UV-Visible Spectrophotometer. AUTHORS :Bhadresh A. Koli*, Pravin N. Sable. METHOD:UV-VIS METHOD ƛmax :233nm Development of Fixed Time Kinetic Spectrophotometric Method for Selective Determination of Metformin in Pharmaceutical Formulations. AUTHORS : SHIVAJI R. LABHADE1*, KAILAS R. LABHADE2 and VISHWAS B.GAIKWAD3 METHOD :UV-VIS METHOD ƛmax:685nm Spectrophotometric determination of metformin hydrochloride via oxidative coupling reaction with 1-naphthol in pharmaceutical and environmental water sample. AUTHOR: Farha Khalaf Omar METHOD:UV-VIS METHOD ƛmax:580nm DEVELOPMENT AND VALIDATION OF UV SPECTROSCOPIC METHOD FOR THE DETERMINATION OF METFORMIN HYDROCHLORIDE IN TABLET DOSAGE FORM AUTHORS: Reatul Karim*, Nurunnahar Poly and Rebecca Banoo METHOD :UV-VIS METHOD ƛmax:233nm
- 9. SECOND DERIVATIVE SPECTROPHOTOMETRIC METHOD FOR THE ESTIMATION OF METFORMIN HYDROCHLORIDE IN BULK AND IN TABLET DOSAGE FORM AUTHORS:NARENDER SHARMA*, ANURAG MISHRA, RAVINDER KUMAR et.al METHOD:UV-VIS METHOD ƛmax :233.8nm Quantitative Determination of Metformin Hydrochloride in Tablet Formulation Containing Croscarmellose Sodium as Disintegrant by HPLC and UV Spectrophotometry AUTHORS:P Umapathi , J.Ayyappan and S Darlin Quine METHOD: HPLC Spectrophotometric Method for Estimation of Metformin Hydrochloride AUTHORS: *Mubeen .G, Khalikha Noor and Vimala M N METHOD : UV-VIS METHOD ƛmax :400nm Spectrophotometric method for analysis of metformin hydrochloride AUTHORS: Mubeen .G, Khalikha Noor METHOD: UV-VIS METHOD ƛmax :570nm
- 10. Drug Profile Pka:12.33 Official status : Indian pharmacopoeia Molecular weight: 129.163g/mol Chemical Formula: C4 H11N5 IUPAC Name: 3- (diaminomethylidene)-1,1- dimethylguanidine CAS number : 657-24-9 Metformin
- 12. Mechanism of action Pharmacokinetices Adverse drug reactions Contraindications It decreases hepatic and renal glucose uptake Absorption: Absorbed over 6 hours ,. Peak action occurs 3 hours after oral administration. Distribution: steady state plasma concentrations of metformin are reached within 24-48 hours. Metabolism: Metformin is not metabolized. Excretion: metformin is excreted unchanged in the urine , T1/2 -1.5 to 3 hrs Duration of action is 8-12 hours More common Nausea, vomiting Abdominal discomfort, Less common Blurred vision Chest discomfort Rare Behavior change similar to being drunk Drowsiness I. Renal disease or renal dysfunction 2. Congestive heart failure requiring pharmacologic treatment. 3. Known hypersensitivity to metformin hydrochloride. 4. Acute or chronic metabolic acidosis
- 13. Need for Study Metformin is a biguanide antihyperglycemic agent used for treating non-insulin dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin mediated glucose uptake. The present work is designed to develop a new validated, simple, rapid, efficient, reliable and economic UV spectrophotometric method for the estimation of metformin from pharmaceutical dosage forms.
- 14. Aim & Objective • To develop a simple, accurate, precise spectrophotometric method. • To optimize and validate the spectrophotometric method as per ICH guidelines.
- 15. Plan of Work Review of literature Selection of drug Solubility Selection of reagents Determination of ƛmax Color development Linearity Assay Analytical method validation
- 16. Materials & Methods Solvents • Distilled water, Methanol, Ethanol, Acetone, Chloroform, Ether, Concentrated Hydrochloric acid , Ferric chloride (1%,2%), Sodium Hydroxide (2%,4%,10%), Sodium Nitrite (10%), ß-Naphthol (1%). Equipments • UV spectrophotometer, • Sonicator • Weighing balance,
- 17. Preparation of metformin standard solution 100mg drug +100ml methanol=1000µg/ml concentration(primary stock) 8,10,12,14,16µg/ml are prepared 100µg/ml(secondary stock) 2ml from each conc. 2-3 drops of conc.Hcl , 10% sodium nitrite , was withdrawn & 10% sodium hydroxide with 1% of ß-naphthol make upto final volume Absorbance was measured maintained at 0°C @ 646nm
- 18. Preparation of metformin sample solution 20 tablets weighed & powdered weighed quantity equivalent to 100mg powder + 100ml methanol 100µg/ml(secondary stock) 1000µg/ml conc.(primary stock) 10µg/ml was prepared 2ml was withdrawn maintained at 0°C 2-3 drops of conc.Hcl , 10% sodium nitrite & 10% sodium hydroxide with 1% of ß-naphthol make upto final volume Absorbance was measured @ 646nm
- 19. Results & Discussion Calibration curve Linearity y = 0.089x - 0.526 R² = 0.9989 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 5 10 15 20 Series1 Series2 Linear (Series1) concentration µg/ml x Absorbancenmy
- 20. Assay of MeforminIn Dosage Form METHOD VALIDATION Accuracy To study the accuracy of the proposed methods, recovery studies were carried out by adding a known amount of drug to the pre analyzed tablet powder and percentage recoveries are calculated. Brand of Drug Label Claim Amount Added Amount of Drug Estimated %Recovery Glyciphage 250 mg 248 mg 244mg 99.2%
- 21. Precision The reproducibility of the proposed method were determined by performing the tablet assay at different time intervals on the same day (intra-day precision) and on three different days (inter-day precision).the results of intra-day and inter-day precisions were expressed in %RSD. Brand of Drug Label Claim Amount Added Amount of Drug Estimated %Recovery % RSD Glyciphage 250 mg 248 mg 244mg 99.2% 0.654
- 22. INTRA-DAY PRECISION INTER-DAY PRECISION Amount µg/ml Amount found %RSD 10 0.351 10 0.356 10 0.354 0.654 10 0.357 10 0.355 10 0.352 Amount µg/ml Amount found %RSD 10 0.352 10 0.357 10 0.354 0.646 10 0.357 10 0.356 10 0.351
- 23. LINEARITY : linear of the range of 8-16 µg/mL. Limit Of Detection And Limit Of Quantification : LOD & LOQ for metformin were found to be 0.0218 µg/ml & 0.066 µg/ml respectively . y = 0.089x - 0.526 R² = 0.9989 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 5 10 15 20 Series1 Series2 Linear (Series1) concentration µg/ml x Absorbancenmy
- 24. Conclusion The absorption maxima was measured at 646 nm and is linear over concentration range 8-16µg/ml. The limits of detection and quantification were calculated to be 0.0218 µg/ml & 0.066 µg/ml respectively The method have been successfully applied for determination of drug in tablet and results obtained are good and percentage drug recovery is 99.2%.
- 25. Bibliography • Review of literature (online)- http://connection.ebscohost.com/c/articles/72102256/ • Review of literature (online)- https://www.academia.edu/9691171 • Review of literature (online)- www.ajptr.co • Drug profile(online) – www.drugbank.com • Drug profile(online) –www.Rxlist.com • Drug profile(online) – www.pubmed.com • Drug profile(online)-www.chemwikki.com • Drug profile(online)- www.webmd.com • Different types of dosage forms of metformin(online)- www.mayoclinic.org • Different types of dosage forms of metformin(online)- www.drugs.com/metformin.html • Different types of dosage forms of metformin(online)- reference.medscape.com • Different types of dosage forms of metformin(online)- www.medicinenet.com • pharmacokinetics of metformin(online)-https://www.pharmgkb.org • pharmacodynamics of metformin(online)- onlinelibrary.wiley.com • pharmacodynamics of metformin (online)-bmcpharmacoltoxicol.biomedcentral.com