Development and Validation of Analytical Methods for Quantitative Estimation of Miglitol

“DEVELOPMENT AND VALIDATION OF ANALYTICAL METHODS FOR QUANTITATIVE ESTIMATION OF MIGLITOL AND METFORMIN IN COMBINED DOSAGE FORMS”

DISSERTATION PROTOCOL

SUBMITTED TO

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

PATEL SEJAL RAMANBHAI

M.PHARM, PART-I

DEPARTMENT OF QUALITY ASSURANCE

NARGUNDCOLLEGE OF PHARMACY

BANGALORE-85

(2010-2012)

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / PATEL SEJAL RAMANBHAI
NARGUND COLLEGE OF PHARMACY,
DATTATREYA NAGAR, II MAIN,
100 FEET RING ROAD,
BSK III STAGE,
BANGALORE-85,
KARNATAKA.
2. /

NAME OF THE INSTITUTION

/ NARGUNDCOLLEGE OF PHARMACY,
DATTATREYA NAGAR, II MAIN,
100 FEET RING ROAD,
BSK III STAGE,
BANGLORE-85,
KARNATAKA.
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN
QUALITY ASSURANCE
4. / DATE OF ADMISSION OF COURSE / 1st JULY 2010
5. /

TITLE OF TOPIC

/ “DEVELOPMENT AND VALIDATION OF ANALYTICAL METHODS FOR QUANTITATIVE ESTIMATION OF MIGLITOL AND METFORMIN IN COMBINED DOSAGE FORMS”
6.
6.1
6.2
6.3
7.
7.1
7.2
7.3
7.4
8. / BRIEF RESUME OF THE INTENDED WORK:
NEED FOR THE STUDY:
Diabetes is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. In the year 2007, the largest amount of people were diagnosed with diabetes were five countries like India(40.9 million), China(38.9 million), US(19.2 million), Russia(9.6 million) and Germany(7.4 million) [1].Type 2 diabetes mellitus is non-insulin dependent diabetes mellitus and it is characterized by insulin resistance which may be combined with relatively reduced insulin secretion[2].
Miglitolis an oral anti-diabetic drug. It reversibally inhibits membrane-bound intestinal alpha-glucoside hydrolyze enzyme which hydrolyzes oligosaccharides and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in delayed glucose absorption and lowering of postprandial hyperglycemia[3].
Metformin is a biguanide class of oral anti-diabetic drugs.It improves hyperglycemia primarily through its suppression of hepatic glucose production and activates AMP-activated protein kinase. It also increases insulin sensitivity, fatty acid oxidation,peripheral glucose uptakeand decreases absorption of glucose from the gastrointestinal tract[1].
Metformin is a frequent first line choice of anti-diabetic medication. But, in monotherapywith any hypoglycemic agent, it is necessary to increase the dose. Because type 2diabetes worsens over time with declining pancreatic beta-cell function and requires addition of a second anti-diabetic medication. Miglitol in combination with Metformin provides a synergistic effect on glycemic control, as indicated by the marked reduction in HbA1c and plasma glucose levels in middle-aged patients in whom type 2 diabetes is insufficiently controlled by diatary management. Combination therapy produced significantly greater reductions in HbA1c, fasting plasma glucose, and particularly postprandial plasma glucose than Metforminmonotherapy[4].
There is no analytical method reported for simultaneous estimation of Miglitol and Metformin. Hence, investigation of new analytical methods is in need for the quantitative estimation of Miglitol and Metformin, in combination in pharmaceutical dosage form.
REVIEW OF LITERATURE :
Miglitol is chemically (2R,3R,4R,5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol andmolecular formula is C8H17NO5and molecular weight is 207.2243g/mol. It issoluble in water [3].
Chemical structure of Miglitol:

[Miglitol]
( I )
Metformin is chemically N,N-dimethylimidodicarbonimidic diamide and molecular formula is C4H11N5andmolecular weight is 129.164g/mol [2]. It is freely soluble in water; slightly soluble in ethanol (95%); practically insoluble in acetone, in chloroform, in dichloromethane and in ether [5].
Chemical structure of Metformin [2] :

[Metformin]
( II )
Ramolia C, Dedania Z, Dedania R,Sheth NR,Vidyasagar G, Patel B and Bhatt KK developed simultaneous estimation of Metformin hydrochloride, Rosiglitazone maleate and Glimepiride in pharmaceutical dosage forms by RP-HPLC method using column RP-C18(2.27μm,250×4.6mm i.d.) and methanol,
acetonitrile,phosphate buffer, pH-5.39(20:40:40% v/v/v) as mobile phase at flow rate 1.0ml/min and at238nm wavelength[6].
Mubeen G, Khalikha N andVimala MN developed spectrophotometric method for estimation of Metformin Hydrochloride which was determined at400nm using distilled water as a solvent [7].
Dhable PN, Seervi CR developed simultaneous UV spectrophotometric method for estimation of Gliclazide and Metformin hydrochloride in tablet dosage form.First method based on solving of simultaneous equation using 228nm(GLZ)and 234nm(MET).Second method based on equation of area under curve at two wavelength regions(233-223nm and 239-229nm)[8].
Dai XM, Ning AN, WU IM, Li HY, Zhang QM reportedHPLC-UV-MS method for the control of four anti-diabetic drugs.An HPLC-UV method has been developed for the determination of Valibose,Miglitol,Voglibose and Acarbose using reversed phase chromatography(prevail carbohydrate column,250mm×4.6mm,5μm)with a gradient acetonitrile,phosphate buffer solution(pH-8.0) in ratio of 80:20 at a wavelength of 210nm[9].
Chittora NC, Shrivastava A, Jain A developed new RP-HPLC method for Miglitol in tablet dosage form suitable for forced degradation studies and estimation in spikedrabbit plasma by Lachrom HPLC with LichrospherODS at ambient temperature with 0.05 M ammonium acetate as mobile phase at a flow rate of 0.5ml/min and measure at 216nm[10].
Arayne MS, Sultana N, Zuberi MH, Siddique FA developed spectrophotometric quantitation of Metformin in bulk drug and pharmaceutical formulations using multivariate technique at five different wavelengths(228nm,230nm,232nm,234nm,236nm)[11].
Lakshmi KS, Rajesh T, Sharma S developed simultaneous determination of Metformin and Pioglitazone by reversed phase HPLC in pharmaceutical dosage formusing a Gemin C18 column (150x4.6mm, 5μ) was used with a mobile phase containing a mixture of acetonitrile and ammonium acetate buffer (pH-3) in the ratio of 42:58. The flow rate was 0.3ml/min and effluents were monitored at 255nm[12].
Sahoo PK, Sharma R, and Chaturvedi SC developed simultaneous estimation of Metformin hydrochloride and Pioglitazone hydrochloride by RP-HPLC method from combined tablet dosage form using acetonitrite:water:acetic acid (60:40:0.3) and pH was adjusted to 5.5 by adding triethylamine and detected at 230nm wavelength and a flow rate was 1ml/min[13].
Xin L,Wang Y,Wang J,Fawcett JP,Zhao L,Jingkai G reported determination of Miglitol in human plasma by liquid chromatography/tandem mass spectrometry using column C18 (5μm,50×4.6mm i.d.) and 10mmol/L ammonium acetate at 1.0ml/min as mobile phase [14].
PatelJR, SuhagiaBN and PatelBH developed simultaneous spectrophotometric estimation of Metformin and Repaglinide in a synthetic mixture by two methods.First method was based on the simultaneous equations,absorbance of both the drugs were detected at 240nm(Metformin) and 291.5nm(Repaglinide). Second method was based on Q-absorbance ratio;absorbances of both the drugs were determined at 240nm(Metformin) and at isoabsorptive point (254.8nm)[15].
OBJECTIVES OF THE STUDY:
Review of literature revealed that there is no analytical method for the simultaneous estimation of Miglitol and Metformin in pharmaceutical dosage form.
Hence the goals of the present work are
To develop different analytical methods to estimate Miglitol and Metformin in combined form by UV-Visible spectrophotometer.
To develop and optimize HPLC method to estimate Miglitol and Metformin in combined dosage form.
To validate the developed methods by ICH guidelines.
MATERIALS AND METHODS:
Materials
Miglitol, Metformin, Miglitol and Metformin Tablets, Double distilled Water, Acetonitrile, Ammonium acetate buffer, Methanol, Acetic acid
Source of data:
Data will be obtained from Science Direct, and other internet facilities, literature search and related articles from library of Nargund College of Pharmacy, Digital Library of RGUHS, Bangalore, etc.
Journals
Asian Journal of Research in Chemistry
International Journal of chem. Tech Research
Journal of young Pharmacists
Indian Journal of Pharmaceutical Science
International Journal of Pharmacy and Pharmaceutical Science
Journal of Pharmacy Research
Text Books and Pharmacopoeia

Beckett AH, Stenlake JB, Practical Pharmaceutical Chemistry. 4th ed.

Delhi: CBS Publisher and Distributors, 1997

Sethi PD, Quantitative Analysis of Drugs in Pharmaceutical Formulation,

3rded. Delhi: CBS Publisher and Distributors

Higuchi T And Brochman E, Hanseen H, Pharmaceutical Analysis, Delhi: CBS Publisher and Distributors, 2005
Mendham J, Denney RC, Barnes JD, Kthomas MJ, Vogel’s text Book of Quantitative Chemical Analysis, 6thed. Pearson education Pvt Ltd, 2002
The Indian Pharmacopoeia, Government of India, Ministry of Health and Family Welfare, Published by The Indian Pharmacopoeia commission Gaziabad, Volume 2, 2007

Internet Browsing
MethodofCollectionofData (IncludingSampling Procedures, IfAny)
Procurement of drugsamples and marketed formulations.
Solubility determination of Miglitol and Metformin in various solvents and buffers.
Studying the spectra of both the drugs in UV–Visible region in different solvents/buffers and selecting the solvents for various analytical studies.
Development of analytical methods by simultaneous equation, absorption ratio, derivative spectroscopy, etc for the estimation of Miglitol and Metforminin combined form by UV-visible spectrophotometer.
Development of HPLC method for estimation of Miglitol and Metformin.
Validation of all developed analytical methods as per ICH guidelines.
Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
- NOT APPLICABLE -
Has ethical clearance been obtained from your institution in case of 7.3?
- NOT APPLICABLE-
LIST OF REFERENCES:
1) (access date Oct 28, 2010).
2) Metformin/ (access date Oct 28, 2010).
3) (access date Oct 28, 2010).
4)Chiasson JL, Naditch L. The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. Diadetes care 2001 June;24(6): 989-94/Miglitol and Metformin.
[Available from
5)Indian Pharmacopoeia, Government of India, Ministry of Health and Family Welfare, Published by the controller of publication, Delhi1996; 1; 469.
6) Ramolia C, Dedania Z, Dedania R,Sheth NR,Vidyasagar G, Patel B and Bhatt KK. Simultaneous estimation of metformin hydrochloride, rosiglitazone maleate and glimepiride in pharmaceutical dosage forms by RP-HPLC method. Asian J Research Chem.2010 Jan-Feb; 3(1): 83-86.
[Available from
7)Mubeen G, Khalikha N andVimala MN. Spectrophotometric method for estimation of metformin Hydrochloride.Int JChemTech Res. 2010April-June;2(2):1186-87.
[Available from
8)Dhable PN andSeervi CR. Simultaneous UV spectrophotometric method for estimation of gliclazide and metformin hydrochloride in tablet dosage form. Int J ChemTech Res.2010 April-June; 2(2): 813-17.
[Available from
9)Dai XM, Ning AN, WU IM, Li HY, Zhang QM. Development and validation of HPLC-UV-MS method for the control of four anti-diabetic drugs. Acta Pharm Sin. 2010; 45:347-52.
[Available from
10)Chittora NC, Shrivastava A, Jain A. New RP-HPLC method of miglitol in tablet dosage form including forced degradation studies and estimation in spiked rabbit plasma. J Young Pharmacists. 2009; 1(4):364-70.
[Available from
11) Arayne MS, Sultana N, Zuberi MH, Siddique FA. Spectrophotometric quantitation of metformin in bulk drug and pharmaceutical formulations using multivariate technique. Indian J Pharm Sci. 2009; 71: 331-35.
[Available from
12)Lakshmi KS,Rajesh T, Sharma S.Simultaneous determination of metformin and pioglitazone by reversed phase HPLC in pharmaceutical dosage form. Int J Pharm Pharmaceut Sci.2009 Oct-Dec; 1(2): 162-66.
[Available from
13)SahooPK, Sharma R and Chaturvedi SC. Simultaneous estimation of metformin hydrochloride and pioglitazone hydrochloride by RP-HPLC method from combined tablet dosage form. Indian J Pharm Sci.2008 May-June; 70(3): 383-86.
[Available from
14)Xin L, Wang Y, Wang J,Fawcett JP,Zhao L,Jingkai G. Determination of miglitol in human plasma by liquid chromatography/tandem mass spectrometry. Rapid communication in Mass spectrometry.2007 Jan; 21(2): 247-51.
[Available from
15)Patel JR, Suhagia BN and Patel BH. Simultaneous spectrophotometric estimation of metformin and repaglinide in a synthetic mixture by two methods. Indian J Pharm Sci. 2007 Nov-Dec; 69(6): 844-46.
[Available from
9. / Signature of the candidate / (PATEL SEJAL RAMANBHAI)
10. / Remarks of the Guide / RECOMMENDED FOR THE DISSERTATION WORK.
11. / Name & Designation of
(in block letters)
11.1Guide
11.2 Signature / DR. L.V.G. NARGUND,
PROFESSOR, HEAD OF THE DEPARTMENT, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, NARGUND COLLEGE OF PHARMACY, BANGALORE.
11.3 Head of the department
11.4 Signature / DR. J. N. NARENDRA SARATH CHANDRA
PROFESSOR, HEAD OF THE DEPARTMENT,
DEPARTMENT OF QUALITY ASSURANCE
NARGUND COLLEGE OF PHARMACY,
BANGALORE.
12. / 12.1 Remarks of Principal
12.2 Signature / FORWARDED AND RECOMMENDED FOR FAVOURABLE CONSIDERATION.