DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF MOXIFLOXACIN AND SPARFLOXACIN
M. PHARM. DISSERTATION PROTOCOL
SUBMITTED TO THE
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.
By,
SHAH KEYURKUMAR ASHOKKUMAR, B .Pharm.
Under the guidance of,
Mr. G.M. SREENIVASA, M. Pharm.
POST GRADUATE DEPARTMENT OF
QUALITY ASSURANCE,
S.C.S. College of Pharmacy,
Harapanahalli – 583131
2009-2010
Rajiv Gandhi University of Health Sciences,
Karnataka, Bangalore.
ANNEXURE II
Name and address of the candidate / SHAH KEYURKUMAR ASHOKKUMAR
NEAR OLD POST OFFICE,
IDAR-383430,
DIST- SABARKANTHA,
GUJARAT.
02 /
Name of the Institution / T.M.A.E. Society’s
S.C.S. College of Pharmacy,
Harapanahalli-583 131,
DIST-Davangere,
Karnataka.
03 / Course of the study / M. Pharm. Quality Assurance
04 / Date of Admission to course / 28th Oct. 2009
05 / Title of the topic / DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF MOXIFLOXACIN AND SPARFLOXACIN
06 / Brief resume of the intended work
6.1 Need for the study /
Enclosure – I
6.2 Review of the Literature / Enclosure – II
6.3 Objective of the Study / Enclosure – III
07 / Materials and Methods
7.1 Source of data /
Enclosure – IV
7.2 Methods of collection of Data / Enclosure – V
7.3 Does the study require any
Investigations on animals?
If Yes give detail / Enclosure - VI
-No-
7.4 Has ethical clearance been
obtained from your Institution
In case of 7.3 /
-Not applicable-
08 / List of References / Enclosure – VII
09 /
Signature of the candidate /
(SHAH KEYUR A.)
10 / Remarks of the guide / The above mentioned title will be carried out in our college, in the Dept. of Quality Assurance under the supervision of Sri. G.M.Sreenivasa.
11 / Name and Designation of
(In Block Letters)
11.1 Guide
Reference no. of RGUHS
ACA/CDC/PGT- M.ph/SCS/02/ 2005 – 06/19.01.09.
11.2 Signature
11.3 Co – Guide
Reference no. of RGUHS
ACA-2/RP-TEA/01/97-98/3-9-98
11.4 Signature
11.5 Head of the Department
11.6 Signature
/
Mr. G.M. SREENIVASA
ASSIS. PROFESSOR
P.G. Dept. Of Quality Assurance
S.C.S. College of Pharmacy
Harapanahalli – 583 131
Dr. E. JAYACHANDRAN
PROFESSOR & HEAD
P.G. Dept. Of Pharmaceutical chemistry
S.C.S. College of Pharmacy
Harapanahalli – 583 131
Dr. R. NAGENDRA RAO
PROFESSOR & HEAD
P.G. Dept. Of Quality Assurance
S.C.S. College of Pharmacy
Harapanahalli – 583 131
12 / Remarks of the Principal
12.1 Signature / The candidate has been permitted to carry out the above said Dissertation Work in the Dept. Of Quality Assurance
06 /
BRIEF RESUME OF THE INTENDED WORK:
ENCLOSURE-I
6.1 Need for the study
Estimation of given drug or medicine in the dosage forms needs the quantitative analysis of that drug or medicine in that dosage form so there are many number of analytical techniques have been developed to fulfil the requirement of estimation. The analytical techniques used are mainly two types,
(a) Chemical analysis
(b) Instrumental analysis
Nowadays there are so many instrumental analysis techniques have been developed with high accuracy and precision with quick result, by using that techniques the quantitative estimation of any drug or medicine in the dosage form can be easily done. Some of the instrumental methods are UV visible spectroscopy, Colorimetry, Turbidimetric and Nephelometric methods, etc1-4.
The above said UV visible spectroscopy method is generally used for estimation or determination of drug, other medicinal compound. Methods5 for estimation of compounds by UV visible spectroscopy are as follows:
1. Assay as a single-component sample
2. Simultaneous equation method
3. Geometric correction method
4. Orthogonal polynomial method
5. Difference spectrophotometry
6. Derivative spectrophotometry
7. Least square approximation
8. Spectrofluorometry method
9. Colorimetric method
The visible spectrophotometry is sometimes called colorimetry6. So by using colorimeter, quantitative analysis can be made of the drug which absorption is in visible range or by forming them into colour solution.
The aim in the present study is to develop a new simple, rapid, reliable, and precise UV spectrophotometric method for analysis.7 Validation is an important feature in any method of measurement because it is closely related to the quality of the results. A method of analysis is characterized by its performance parameters, which have to be assessed if they are to provide the correct performance values.
These performance values must be in accordance with previously defined requirements that the method of analysis should satisfy8.
Method of validation is the process used to confirm that the analytical procedure employed for a specific test is suitable for its intended use. Results from method validation can be used to judge the quality, reliability and consistency of
analytical results; It is an integral part of any good analytical practice9.
Analytical methods need to be validated and revalidated
· Before their introduction into routine use;
· Whenever the conditions change for which the method has been validated (e.g. an instrument with different characteristic and sample with a different matrix); and
· Whenever the method is changed and the change is outside the
original scope of the method
Antimicrobial drugs are the greatest contribution of the 20th century to therapeutics. Their advent changed the outlook of the physician about the power drugs can have on diseases. They are one of the few curative drugs. Their importance is magnified in the developing countries, where infective diseases predominate. As a class they are one of the most frequently used as well as misused drugs.10
Antimicrobial therapy takes advantage of the biochemical differences that exist between microorganisms and human beings. Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity; that is, they have the ability to injure or kill an invading microorganism without harming the cells of the host. In the most instances, the selective toxicity is relative rather than absolute, requiring that the concentration of the drug be carefully controlled to attack the microorganism while still being tolerated by the host.11
Moxifloxacin12 is a synthetic fluoroquinolone antibiotic agent. The chemical IUPAC name is 7-[(4aS,7aS)-1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid and molecular formula is C21H24FN3O. Average molecular weight is 401.4314.
MOXIFLOXACIN
Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.
Moxifloxacin13 is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: Corynebacterium species, Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri, Streptococcus pneumoniae, and Streptococcus viridans group. Aerobic Gram-negative microorganisms: Acinetobacter lwoffii, Haemophilus influenzae, and Haemophilus parainfluenzae. Other microorganisms: Chlamydiatrachomatis.
For the treatment of sinus and lung infections such as sinusitis, pneumonia, and secondary infections in chronic bronchitis. Also for the treatment of bacterial conjunctivitis (pinkeye).
Sparfloxacin14 is a fluoroquinolone antibiotic used in the treatment of bacterial infections. The chemical IUPAC name is 5-amino-1-cyclopropyl-7-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid and molecular formula is C19H22F2N4O3 and Average molecular weigh 392.3998
SPARFLOXACIN
Sparfloxacin is a synthetic fluoroquinolone broad-spectrum antimicrobial agent in the same class as Ofloxacin and Norfloxacin. Sparfloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms. Quinolones differ in chemical structure and mode of action from (beta)-lactam
antibiotics. Quinolones may, therefore, be active against bacteria resistant to (beta)-lactam antibiotics. Although cross-resistance has been observed between Sparfloxacin and other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to Sparfloxacin. In vitro tests show that the combination of Sparfloxacin and Rifampin is antagonistic against Staphylococcus aureus.
The bactericidal15 action of Sparfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial
DNA replication, transcription, repair, and recombination.
For the treatment of adults with the following infections caused by susceptible strains microorganisms: community-acquired pneumonia (caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae) and acute bacterial exacerbations of chronic bronchitis (caused by Chlamydia pneumoniae, Enterobacter cloacae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumonia)
ENCLOSURE - II
6.2 Review of literature
The review of various published work related to subject and objectives of the study has revealed the following:
Ø Patel Kamlesh, Badmanaban R, Patel CN; Development and Validation of Spectrophotometric methods for the Estimation of Sparfloxacin in Tablet Dosage Forms, Journal of Chemical and Pharmaceutical, 2010, 2(1): 528-532.
Ø Herida R. N. Marona and Elfrides E.S. Schapoval; Spectrophotometric determination of Sparfloxacin in pharmaceutical formulations using Bromothymol blue, Journal of Pharmaceutical and Biomedical Analysis, Oct 2001, Volume 26, issue 3, ,Pages 501-504.
Ø A.V. Subbayamma; Spectrophotometric determination of Cefpodoxime Proxe til in Tablets, Asian Journal of Chemistry, No. 5(2010), vol. 22, 3345-3348.
Ø N.Sreekanth; A new colorimetric determination and validation of
Sparfloxacin based on ferric nitrare chromogen, Research Journal of
pharmaceutical, Biological and chemical sciences, April - June 2010, vol.1,
Issue-2.
Ø Motwani SK; Validated Spectrophotometric methods for the estimation of
Moxifloxacin in bulk and pharmaceutical formulations, Spectrochimica Acta
Part A: Molecular and Biomolecular Spectroscopy, October 2007, vol 68,
Issue-2,Pg.no-250-256.
Ø H.R.N. Salgado; Development and Validation of an UV spectrophotometric method for determination of Gatifloxacin in tablets, Pharmazia, April 2005, Vol:60,Issue:4,Pg.no.263-264.
Ø Srikar A* et al.; Spectrophotometric estimation of Sparfloxacin in Bulk and Pharmaceutical dosage forms, International Journal of Pharmacy and technology,March-2010,Vol.2,Issue-1,Pg.No.16-22.
ENCLOSURE - III
6.3 MAIN OBJECTIVE OF THE STUDY
The present work is in an attempt to:
1. To develop selective, precise and sensitive method for the development and estimation of the Moxifloxacin and Sparfloxacin.
2. The analytical method so far developed is to be validated.
3. The work involves use of analytical techniques such as Spectroscopy.
4. The method appears to be suitable for the quality control in pharmaceutical industry.
07 /
MATERIALS AND METHODS
ENCLOSURE - IV
7.1 SOURCE OF DATA.
The primary data required for designing the work will be collected from
1. Various national and international journals available in college library.
2. From various open access journals available in internet.
3. From helinet service of RGUHS, Bangalore.
4. From various reference books available in college library.
5. From various search engines like google.com, ask.com etc.,
6. By referring various journals from libraries of Indian Institute of Science, Bangalore, Libraries of various Universities like Manipal University, Manipal, Karnataka University, Dharwad.
7. Bu using various Pharmacopoeia like Indian Pharmacopoeia, British Pharmacopoeia, United States Pharmacopoeia, etc.
ENCLOSURE – V
7.2 METHODS OF COLLECTION OF DATA
Data pertaining for the present study will be obtained from Quality Assurance Laboratory of S.C.S College of Pharmacy, Chemical abstracts, Scientific abstracts, Journals and Internet sources etc.
ENCLOSURE - VI
7.3 Does the study require any investigation to be conducted on
patients/Humans/ Animals? If so describe briefly
-No-
7.4 Has ethical clearance been obtained from your institution in
case of
-Not Applicable-
08 /
ENCLOSURE - VI
REFERENCES
1. Srikar A, Channabasavaraj K.P., Dharmamoorty G, Nataraj V, Chinnappa
C and Venu T, Spectrophotometric method for Quantitative Estimation of
Sparfloxacin in Bulk and Pharmaceutical Dosage forms, Journal of
Pharmaceutical Sciences and Research, 2009,Vol.1(2), Pg. no. 13-15.
2. Ravindra Rao K., Vijaya Ratna J, and Manikya Rao T, Comparative
Bioavailability of four marketed Sparfloxacin Formulations in Healthy Human
Volunteers, E-Journal of Chemistry, Mar. 2004, Vol. 1, No. 1, Pg no. 43-50.
3. Filiz SAYIN, Sedef KIR, Determination of Diflunisal in Tablets Using
Derivative UV Spectrophotometric Methods, FABAD J. Pharm. Sci., 2004, 29,
121-126.
4. Al-Ghannam SM, Atomic absorption spectroscopic, conductometric and
colorimetric methods for determination of some fluoroquinolone antibacterials
using ammonium reineckate, Spectrochim Acta A Mol Biomol Spectrosc.
Apr.2008;69(4):1188-94.Epub2007,Jun-28.
5. Spectroscopy – Wikipedia the free encyclopedia.
6. Mendham J, Denney RC, Barnes JD, Thomas MJK, Vogel’s, Textbook of
Quantitative Chemical Analysis, Sixth Edition, Pg. no. 6.
7. Shah R, Chandrakant Magdum, Shital Kumar, Dhanya Kumar Chougule and
Nilofer Naikwade, Reasearch Journal of Pharmacy and Technology ,Oct.-
Dec. 2008, 1(4).
8. European medicines Agency, ICH Topic Q 2 (R1) Validation of analytical
procedures: Text and Methodology.
9. Gomes GC & Hérida Regina Nunes SALGADO, Validation of UV
Spectrophotometric Method for Determination of Lomefloxacin in
Pharmaceutical Dosage Form, Acta Farm. Bonaerense, 2005, 24 (3): 406-8
10. Tripathi KD, Essentials of Medical Pharmacology, Sixth Edition, Pg. no. 66.
11. Richard A. Harvey, Pamela C. Champe, Lippincott’s illustrated reviews
Pharmacology 4th edition, Pg. No. 447
12. Drug Bank Showing Moxifloxacin (DB00218).mht.
13. Moxifloxacin – Wikipedia the free encyclopedia.
14. Drug Bank Showing Sparfloxacin (DB01208).mht.
Sparfloxacin – Wikipedia the free encyclopedia