3) Project Work Power Point

ByG.Hemasree (Y7PH2211)M.Harsha (Y7PH2224)P.Nagaraju (Y7PH2232)P.Praveen (Y7PH2238)SK.M.Subhani (Y7PH2248)Ch.Anil Babu (L8PH2260)

Under the guidance of Mr.I.Srikanth

M.Pharm

DRUG PROFILE & LITERATURE REVIEW

EXPERIMENTAL WORK

VALIDATION SUMMARY REPORT

SUMMARY & CONCLUSION

DRUG PROFILE

Chemical Structure:    

Chemical Name: (±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2- methoxyphenoxy)ethyl]amine

Molecular Formula: C24H26N2O4

 Molecular Weight: 406.5 Characteristics: White or off – white crystalline powder .    Solubility: Insoluble in Water.

Carvedilol

Soluble in Methanol & Methylene chloride. Free soluble in Dimethyl sulfoxide.

Mechanism of Action

Carvedilol is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomers and α1-adrenergic blocking activity is present in both R (+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity.

Pharmacokinetics

Bioavailability : 25-35%Protein Binding : 98%Metabolism : Hepatic (cyp 2D6, cyp 2c9)Half Life : 7-10 hoursExcretion : Renal 16%, Fecal 60%

Therapeutic Uses

1. High Blood Pressure.

2. Heart Disease. Dosage

Patients Weighing < 85 kg (187 lb): 25 mg twice daily. Patients Weighing > 85 kg (187 lb): 50 mg twice daily.

How to Use :

3.125 mg taken twice daily for two weeks. This dosage is same regardless of the age of weight of the patient. Carvedilol should be taken with food. Patient should be observed in the office for one hour after initial dose is given.

Storage : Store in a close, cool & light resistance container.

Brand Names : Cardivas (Tablets), Coreg (Tablets).

Review of Literature

Gita Chaursia, et al : Two simple, fast convinient, precise, reproducible UV spectrophotometric methods have been developed for the determination of carvedilol in pure form in tablets using methanol (method A) and Polyethylene glycol-400:water(2:1) (method B). The UV spectrum of carvedilol showed absorption maxima at 242 nm and 245 nm, respectively in methanol and PEG-400: water (2:1). Good agreement with Beer’s law was found in the range of 2 to 20 µg/ml for method-A and 1to 10 µg/ml for method-B.

P.S.Jain, et al : A new simple, sensitive spectrophotometric method in ultraviolet region has been developed for the determination of carvedilol in bulk and pharmaceutical formulations. Carvedilol exhibited maximum absorbance at 285 nm with apparent molar absorptivity of 15.4x10 l/mol.cm in methanol. Beer’s law was found to be obeyed in the concentration range of 4-36µg/ml. Results of the analysis were validated stastically and by recovery studies.

J. K. Verma, et al : A sensitive and rapid extractive spectrophotometer method has been developed for the assay of carvedilol in pharmaceutical formulations. The method is based on the formation of a chloroform soluble ion-pair complex between carvedilol and bromocresol green in an acidic medium. The complex shows absorption maximum at 415 nm and the system obeys Beer’s law in the concentration range of 5-25 µg/ml. The results obtained by the proposed method were validated statistically and by recovery studies.

Navneet Verma, et al : The present investigation deals with the development of a new, simple specific, sensitive, rapid and economical procedure for simultaneous estimation of Carvedilol in its dosage form. The method is based on the ultraviolet absorbance maxima of the above drug at 285 nm. The drug obeyed Beer's law in the concentration range of 4-36 µg/ml with molar absorptivity of 12.6x 103 l/mol.cm in methanol. The proposed methods were successfully applied for the simultaneous determination of drug in commercial tablet preparations. The results of the analysis have been validated statistically and by recovery studies.

EXPERIMENTAL WORK

ESTIMATION OF CARVEDILOL BY UV SPECTROPHOTOMETRY

ESTIMATION OF CARVEDILOL BY VISIBLE SPECTROPHOTOMETRY

METHOD – A

METHOD - B

Instrumentation used for the Study: ELICO SL 210 model with Double beam UV Visible spectrophotometer.

ESTIMATION OF CARVEDILOL BY UV SPECTROPHOTOMETRY

Selection of solvent

Determination of λmax Preparation of calibration curve

Analysis of formulation

Recovery studies

Preparation of Stock solution

S.NO.

Concentration

(µg/ml)

Wavelength(nm)

Absorbance

1. 10 215 0.10402. 10 220 0.10493. 10 225 0.10584. 10 230 0.10645. 10 235 0.10766. 10 240 0.10827. 10 245 0.10908. 10 250 0.10819. 10 255 0.1072

10. 10 260 0.106711. 10 265 0.1052

Selection of λ max

TABLE -1

A Representative Spectrogram for Carvedilol

UV SPECTROPHOTOMETRY

S.NO Concentration

(µg/ml)

Wavelength(nm)

Absorbance

1. 10 230 0.1063

2. 10 235 0.1079

3. 10 240 0.1086

4. 10 245 0.1090

5. 10 250 0.1088

6. 10 255 0.1076

7. 10 260 0.1069

8. 10 265 0.1061

9. 10 270 0.1056

TABLE -2

A Representative Spectrogram for Carvedilol

Preparation of Calibration Curve

S.NO Concentration(µg/ml) Absorbance 1. 10 0.12062. 20 0.27453. 30 0.52564. 40 0.73185. 50 0.85206. 60 0.9987

S.NOConcentration

taken for analysis(µg/ml)

Amount of substance

found(µg/ml)

%Recovery*

1. 30 29.18 97.262. 40 39.97 99.923. 50 50.52 101.10

Mean %recovery

99.42

Analysis of Formulation

A Representative Calibration curve for Carvedilol

Recovery Studies

S. No

LevelConcentration of standard used(µg/ml)

Concentration of sample used(µg/ml)

Amount found

(µg/ml)

%Recovery

1. Solution-A

30 30 29.18 97.26

2. Solution-B

40 40 39.97 99.92

3. Solution-C

50 50 50.52 101.10

Mean % Recovery 99.42

Selection of solvent

Selection of Chromogenic agent

Preparation of Stock solution

Determination of λmax

Preparation of Calibration Curve

Analysis of Formulation

Recovery Studies

ESTIMATION OF CARVEDILOL BY VISIBLE SPECTROPHOTOMETRY

METHOD – A

Selection of λ max

S.NO Concentration

(µg/ml)

Wavelength(nm)

Absorbance

1. 100 400 0.3262. 100 405 0.4873. 100 410 0.4394. 100 415 0.3895. 100 420 0.355

S.NO Concentration

(µg/ml)

Wavelength(nm) Absorbance

1. 100 400 0.4392. 100 405 0.4893. 100 410 0.4704. 100 415 0.4625. 100 420 0.445

TABLE – 1

TABLE - 2

A Representative Spectrogram for Carvedilol

VISIBLE SPECTROPHOTOMETRY

METHOD - A

A Representative Spectrogram for Carvedilol

Calibration Curve

S.NO Concentration(µg/ml) Absorbance

1. 100 0.090

2. 200 0.153

3. 300 0.267

4. 400 0.379

5. 500 0.411

6. 600 0.531

A Representative Calibration curve for Carvedilol

Analysis of Formulation

S.NOConcentration

taken for analysis(µg/m

l)

Amount of substance

found(µg/ml)

%Recovery

1. 200 197.13 98.562. 400 398.52 99.633. 600 602.74 100.45

Mean %recovery 99.6 Recovery Studies

S. No

LevelConcentratio

n of standard

used(µg/ml)

Concentration of

sample used(µg/ml)

Amount found

(µg/ml)

%Recovery*

1. Solution-A

200 200 197.13 98.56

2. Solution-B

400 400 398.52 99.63

3. Solution-C

600 600 602.74 100.45

Mean %Recovery 99.6

ESTIMATION OF CARVEDILOL BY VISIBLE SPECTROPHOTOMETRY

METHOD – B

Selection of solvent

Selection of Chromogenic agent

Determination of λmax

Preparation of Stock solution

Preparation of Calibration Curve

Analysis of Formulation

Recovery Studies

Selection of λ max

TABLE - 1

S.NOConcentratio

n(µg/ml)

Wavelength(nm)

Absorbance

1. 100 490 0.3262. 100 500 0.3553. 100 510 0.3674. 100 520 0.3775. 100 530 0.3896. 100 540 0.4127. 100 550 0.439

8. 100 560 0.487 9. 100 570 0.443 10. 100 580 0.419

A Representative Spectrogram for Carvedilol

VISIBLE SPECTROPHOTOMETRY

METHOD - B

A Representative Spectrogram for Carvedilol

Calibration Curve

S.NO Concentration(µg/ml) Absorbance1. 100 0.1022. 200 0.2103. 300 0.3114. 400 0.4545. 500 0.504

6 600 0.674

Analysis of Formulation

S.NOConcentration

taken for analysis(µg/m

l)

Amount of substance found(µg/

ml)

%Recovery

1. 200 198.62 99.652. 400 399.61 99.933. 600 602.74 100.34

Mean %recovery 99.97

A Representative Calibration curve for Carvedilol

Recovery Studies

S. No LevelConcentrati

on of standard

used(µg/ml)

Concentration of

sample used(µg/ml)

Amount found

(µg/ml)

%Recovery

1. Solution-A

200 200 198.62 99.65

2. Solution-B

400 400 399.61 99.93

3. Solution-C

600 600 602.74 100.34

Mean %Recover

y

99.97

VALIDATION SUMMARY REPORT

S.NO PARAMETER RESULTS

UV COLORIMETRY

METHOD-A

COLORIMETR

Y

METHOD-B

1 Linearity

range

(µg/ml)

10-60µg/ml 100-600 µg/ml 100-600

µg/ml

2 Correlation

coefficient (r)

0.9936 0.9925 0.9945

3 R2 0.9874 0.9851 0.9985

4 Intercept 0.0572 0.0459 0.0473

5 Slope 0.018307 0.029631 0.022603

6 Standard

deviation (SD)

0.2239 0.2784 0.3194

7 Standard error

(SE)

0.0132 0.0212 0.0231

8 Limit of detection

(LOD) (ng/ml) 931.04 181.72 185.197

9 Limit of

Quantification

(LOQ) (ng/ml)

3125.682 2981.467 2220.559

10 % RSD 0.7784 0.6441 0.7953

11 Intra day (%RSD) 0.01 0.0055 0.0067

12 Inter day (%RSD) 0.00725 0.0176 0.02695

13 Repeatability

(%RSD)

0.0091 0.0105 0.0111

14 Accuracy 99.42% 99.6% 99.97%

SUMMARY & CONCLUSION

The methods discussed in the present work provide a convenient and accurate way for estimation of Carvedilol. Percent label claim for Carvedilol in tablet by all the three methods, was found in the range of 99.97% to 100.253%. Standard deviation and percentage RSD for six determinations of tablet sample by both the methods was found to be less than ±2.0 indicating the precision of both the methods. Accuracy of proposed methods was ascertained by recovery studies and the results are expressed in Mean % recovery. Mean percent recovery for Carvedilol was found in the range of 99.42% to 99.97%, values of standard deviation and % RSD were in the range of ±0.2239 to ±0.3194 and 0.6441 to 0.7953 respectively indicating the accuracy of the proposed methods. Based on the results obtained, it is found that the proposed methods are accurate, precise, reproducible and economical methods for the estimation of Carvedilol in Bulk drug and its Pharmaceutical formulations.

REFERENCES

• Day, R.A,JR, Underwood, A.L., Quantitative Analysis, 6th Edition, Prentice-Hall of India Pvt. Ltd, New Delhi,1993,1.

• Galen, W.E., Instrumental Methods of Chemical Analysis., 5th Edition, Mc.Grew-Hill International Editions,1.

• Gary, D.C., Analytical Chemistry., 6th Edition., 1.

• Gurnee R.C., Instrumental Methods of Chemical Analysis, 5th Edition, 5th Revised and Enlarged Edition, Himalaya Publishing House, 2002, 1

• Sethi P.D., Quantitative Analysis of Drugs in Pharmaceutical Formulations, 3rd Edition, 1997, 1.• Varasha pokharkar, Abhishek Khanna, Vinod Venkatpurwar Sheetal dhar, Leenatamandpe, Ternary complexation of Carvedilol-Cyclodextrin and Citrc acid mouth dissolving tablet formulation, Acta Pharm. 59 (2009) 121–132. • M L Varahala Setti, J Vijaya Ratna, Preparation and Evaluation of control release tablets of Carvedilol, Asian journal of pharmaceutics, 252-256, 2009.

• Githa Chaurasia, D. Bhadra, S.Bhadra & N.K.Jain, UV Spectroscopic Determination of Carvedilol, Indian journal of pharmaceutical sciences , 606-607, 2005.

• P.S.Jain, G.S.Taleele & S.J.Surana, Spectroscopic Determination of Carvedilol from bulk and formulation, Indian journal of pharmaceutical sciences, 308-309, 2005.

• Navneet Verma*1, A. K. Ghosh 1 and P. Chattopadhyay Simultaneous Spectrophotomeric Determination of Carvedilol in its dosage form, International journal of pharmaceutical sciences & research 188-190, 2010.

• Dr.C.Theivarasu, Santanu Ghosh & T.Indumathi UV Spectrophotometric Determination of Cavedilol in pharmaceutical formulations, Asian journal of pharmaceutical & clinical research, 64-68, 2010.• Rau´ l A. Silvaa, Chien ChunWangd, Liliana P. Ferna´ndezb,d, Adriana N. Masi c,d, Flow injection spectrofluorimetric determination of carvedilol mediated by micelles A Journal of talanta, 166-171, 2008.