“INVESTIGATION OF validated ANALYTICAL METHODS FOR the QUANTITATIVE ESTIMATION OF SOMEANTI-INFLAMMATORY DRUGS”

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

By

VENUGOPAL DARAK.

Under the guidance of

Mr. ARVIND.B.KARADI

M. Pharm, (Ph.D).

DEPARTMENT OF PHARMACEUTICAL

ANALYSIS

H.K.E.S’s COLLEGE OF PHARMACY

GULBARGA-585105

2009-10
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF Subjects FOR DISSERTATION

1. / Name of the Candidate and
Address (in block letters) / venugopal darak
s/o rameswar darak
c/o r. r .darak main road
at post guledgudd 587203 dist-bagalkot
2. / Name of the Institution / H.K.E.S’s College of Pharmacy, Sedam Road, GULBARGA-585105 (Karnataka)
3. / Course of Study and Subject / M. Pharm. (Pharmaceutical Analysis)
4. / Date of Admission to Course / 20-6-2009
5. / Title of the Research Topic / “INVESTIGATION OF VALIDATED ANALYTICAL METHODS FOR THE QUANTITATIVE ESTIMATION OF SOME ANTI-INFLAMMATORY DRUGS”
6. /

BRIEF RESUME OF INTENDED WORK

6.1 Need for Study

Mesalamine is used because of its Local effect in the treatment of inflammatory bowel disease exogenous. It is official in United State Pharmacopoeia (USP). Investigations of some new analytical methods are in need for the quantitative estimation of Mesalamine in bulk drug and pharmaceutical dosage forms with high sensitivity, accuracy, precision and economical.

6.2Review of Literature

Mesalamine1-2is chemically Benzoic acid,5-amino-2-hydroxy-5-aminosalicylic acid. The molecular formula ofMesalamine is C7H7NO3, molecular weight is 153.14,C 54.90%, H 4.61%, N 9.15%, O 31.34%.Melting point is 280C. It is slightly soluble in cold water, more soluble in hot water; soluble in HCl.
Mesalamine3 also known as Mesalazine is an anti-inflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative colitis. Mesalazine is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having less systemic side effects. As a derivative of salicylic acid, 5-ASA is also an antioxidant that traps free radicals, which are potentially damaging by-products of metabolism.
Although the mechanism of action of Mesalazine is not fully understood, it appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.
A few methods were reported for the determination of Mesalamine by spectrophotometry4-5 and HPLC6-7.

6.3 Objective of Study
Since, very few analytical methods have been reported for the quantitative estimation of Mesalamine, there is a necessity for investigation of new analytical methods for the quantitative estimation of Mesalamine in bulk drug and pharmaceutical dosage forms (tablets). In view of the above facts, the following analytical methods are planned to develop.

R – NH2
(I)

i) Since, mesalamine (I) is having aromatic amino group it can be condensed with various aldehydes like p-dimethylaminobenzaldehyde (PDAB) (II), p-dimethylcinnamaldehyde (PDAC)(III)to get coloured Schiff’s bases and can be used for quantitative estimation of drug by visible spectrophotometry.



Mesalamine (I) canbe condensed withVanillin to get coloured Schiff’s base and can be used for quantitative estimation of drug by visible spectrophotometry.

ii) Aromatic amino group can be diazotised with nitrous acid (HNO2) and the diazonium salt can be coupled with Chromogenic agents like N-(l-napthyl) Ethelenediamine Dihydrochloride (B M Reagent IV),to get coloured chromogen (V) and drug can be estimated quantitatively by colorimetry.

The diazonium salt can also be coupled with -napthol, napthalamine, Diphenylamine, chromotropic acid and Phloroglucinol to get coloured chromogens to estimate the drug colorimetrically
iii) The amino group in Mesalamine allows the oxidative coupling reaction with 3-Methyl-2-Benzothiazolinone Hydrazone (MBTH) in presence of Ferric Chloride/Cerric ammonium sulphate and forms colored chromogen (VI) by which drug can estimated quantitatively by colorimetry.

iv) Phosphomolybdotungstic acid well known as Folin-Ciocalteu reagent,forms coloured chromogen with Mesalamine in alkaline PH due to presence of aromatic amino group by redox reaction which can be used for quantitative estimation of Mesalamine in bulk drug and its pharmaceutical formulations.
v) Mesalamine forms coloured complexs (VII, VIII) with 1,10-Phenanthroline and 2,2l-Bipyridine in presence of Fe3+ion which can be utilized for quantitative estimation of Mesalamine in pharmaceutical formulation.

vi) Visible spectrophotometric methods can also be developed using chromogenic reagent like Gibbs reagent due to presence of amino group in Mesalamine.
vii) RP HPLC methods can also be developed.
viii) Various HPTLC methods can also be developed.
ix) Simultaneous estimation methods can also be developed.
7. MATERIAL AND METHODS
In the present work investigation of some new instrumental methods for quantitative estimation of Mesalamine, we are in need and using Shimadzu 1700 double beam UV/visible spectrophotometer, HPLC (Shimadzu class vp series 6.01), Chromatographic instruments and volumetric glass apparatus. Drug sample will be collected from Sun pharmaceutical Ltd, Bari brahmana Jammu-18113.
7.1 Source of Data
a)Internet, Library.
b)Gulbarga University, Gulbarga.
c)I.I.Sc. Library, Bangalore
d)I.I.C.T. Library, Hyderabad
e)R.G.U.H.S. Library, Bangalore.
7.2 Methods of Collection of Data (including sampling procedure, if any)
Data collected from
  1. Internet, H.K.E.S’s. College of Pharmacy, Gulbarga.
  2. Analytical abstract and chemical abstract Gulbarga University, I.I.C.T. & I.I.SC. Libraries.
  3. Journals like – Indian J. Pharmaceutical Sciences, Indian Drug & Indian J. Analytical Chemistry.
  4. e-Journals
v. Drug sample of mesalamine will be collected from Sun pharmaceutical Ltd, Jammu.
7.3Does study require any investigation or interventions to be conducted on patients or other humans or animals? If so please describe briefly
-No-

7.4 Has ethical clearance been obtained from your institution in case of 7.3
-Not Applicable-

REFERENCES

  1. O’ Neil MJ, editor. The Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals. 14th edn, Merck & Co. Inc.: 2006;613.
  2. Sweetman SC, editor. Martindale: The Complete Drug Reference, 35th edn, Pharmaceutical Press: London (U.K): 2007;1573.
  3. Bertam G Katzung, editor. Basic and Clinical Pharmacology, 9th edn. Mc. Graw Hill, Singapore, 2007; 1030.
  4. Aleka K. Dashand Harry G. Brittain. Analytical Profile of Drug Substances and Excipients, Brittain:1998;25: 209-42.
  5. Prakash A, Lone KD, Shukla A, Mandloi R and Ghosh V. Asian J Research Chem: 2008 ;1(2): 80-82.
  6. The United State Pharmacopeial Convection, editor.United State Pharmacopeia. NF, Asian edn: 2007; 03: 2584.
  7. Janice Aparecida Rafael, Jose Robert Jabor, Rubia Casagrande, Maria Jose Vieira Fonseca Et al. Brazilian Journal of Pharmaceutical Sciences 2007;43(1): 97-103.

9. / Signature of Candidate
10. / Remarks of the Guide / The work undertaken is industrial oriented and can be considered for quality control in Drug Analysis.
11. / Name & Designation of (in block letters)
11.1Guide.
11.2Signature / Mr. ARVIND.B.KARADIM.Pharm, (Ph.D)
ASST PROFESSOR
DEPT. OF PHARMACEUTICAL ANALYSIS, H.K.E.S’s COLLEGE OF PHARMACY, GULBARGA.
/ 11.3Head of the Department.
11.4Signature / Dr. S.M.MALIPATIL, M.Pharm, Ph.D
PROFESSOR
DEPT. OF PHARMACEUTICAL ANALYSIS, H.K.E.S’s COLLEGE OF PHARMACY, GULBARGA.
12. / 12.1Remarks of the Chairman & Principal.
12.2 Signature.