“DEVELOPMENT AND VALIDATION OF STABILITY INDICATING HPLC METHOD FOR DESLORATIDINE IN PHARMACEUTICAL DOSAGE FORMS”

DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

BY

PATEL AVINASHBHAI HASMUKHLAL

M.PHARM, PART-I

DEPARTMENT OF QUALITY ASSURANCE

NARGUND COLLEGE OF PHARMACY

BANGALORE-85

(2010-2012)

RAJIV GANDHI UNIVERSITY 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 AVINASHBHAI HASMUKHLAL
NARGUND COLLEGE OF PHARMACY,
DATTATREYA NAGAR, II MAIN,
100 FEET RING ROAD,
BSK III STAGE,
BANGALORE-85,
KARNATAKA.
2. /

NAME OF THE INSTITUTION

/ NARGUND COLLEGE 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 STABILITY INDICATING HPLC METHOD FOR DESLORATIDINE IN PHARMACEUTICAL 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:
The pharmaceutical industry is always under increased scrutiny to constrain costs and yet consistently deliver to market safe, efficacious products that fulfil medical needs. As a part of this, drug analysis plays an important role for assuring quality of pharmaceutical product throughout its shelf life and also better understanding of physiochemical properties of pharmaceutical compounds using advanced instrumental methods. Standard analytical procedure for newer drugs or formulations may not be available in the pharmacopoeia; hence it is essential to develop an analytical method for newer drugs or formulations, which is accurate, precise, specific, linear, simple and rapid.
Desloratadine (descarboethoxyloratadine), invented in 2005, is a non sedative metabolite of Loratadine, a second generation long acting antihistaminic drug with selective peripheral H1 receptor antagonistic activity [1]. Desloratadine is available in different dosage forms like tablet and syrup. It has demonstrated antiallergic properties from in vitro studies. These include inhibiting the release of pro-inflammatory cytokines such as IL-4, IL-6, IL-8 and IL-13 from human mast cells/ basophilic as well as inhibition of the expression of the adhesion molecule P-selection on Endothelial cells.[2]
Extensive literature survey revealed that there were a few methods reported for estimation of desloratadine from plasma and from pharmaceutical dosage forms. Therefore here an attempt was made to develop simple, and more cost effective, sensitive and specific HPLC method for desloratadine.
REVIEW OF LITERATURE :
Ø  Chemically Desloratidine is 8-chloro-6, 11-dihydro-11-(4-piperdinylidene)-5H-benzo [5, 6] cyclohepta [1, 2-b] pyridine. Molecular formula is C19H19ClN2 and molecular weight is 310.82 g/mol. It is slightly soluble in water, very soluble in ethanol and propylene glycol.[3]
Ø  NOTE: Canadian product information lists freely soluble in ethanol, methanol, methylene chloride, and octanol; very slightly soluble in water; soluble in 0.1N hydrochloric acid, and dimethyl sulfoxide; slightly soluble in pH 7.4 phosphate buffer; practically insoluble in 0.1N sodium hydroxide.[4]
Ø  Chemical structure of Desloratidine.

Desloratidine[3]
( I )
Ø  Bondili S, Reddy SP developed spectroscopic method for determination of Desloratidine in bulk and its tablet dosage forms using methanol as solvent. Detection was carried at 242 nm.[1]
Ø  Alam Razib M, Md. Ullah A, Mohammad Azad AK, Sultana R, Yasmin H and Hasnat A developed RP-HPLC Method for the quantification of Desloratadine in pharmaceutical dosage forms using the reverse phase C18 column (250 mm × 3.3 mm I.D., 5μm particle size) and mobile phase containing acetonitrile ׃ n-pentane sulphonic acid sodium salt monohydrate in the ratio of 60:40(v/v) (pH 3.0± 0.05). Flow rate was kept at 1 ml/min and elution was monitored at 254 nm.[2]
Ø  Gajjela R, Yalavarthi R, VYAS K, Mulukutla VS, Khagga M developed a new validated Liquid Chromatographic method for the determination of Loratadine and its impurities by using Inertsil ODS-3V, 250 x 4.6 mm, 5μ column, mobile phase containing Buffer (0.05 M monobasic potassium phosphate), Acetonitrile, Methanol and Triethyl amine (38:45:17:0.5 v/v) adjusted with ortho phosphoric acid to a pH of 3.6. Flow rate was kept at 1.0 mL min−1 and UV detection was performed at 220 nm.[5]
Ø  Mallapu Rani E, Ahad HA, Sreenivasulu R, Rani M, Mandava G, Reddy B. KK, Kranthi G developed spectrophotometric method for determination of Desloratidine in pharmaceuticals by using strong basic media at two wavelength 215 nm and 453 nm.[6]
Ø  Walash MI,F. Belal F,El-Enany N,Eid M,El-Shaheny RN developed stability-indicating micelle-enhanced spectrofluorimetric method for determination of loratadine and desloratadine in dosage forms by using sodium dodecyl sulphate (SDS) micellar system with acetate buffer solvent of pH 4.5. The fluorescence intensity was measured at 438 nm after excitation at 290 nm for both drugs.[7]
Ø  Dantu DR, Satyanarayana NV, Reddy AM, Sait SS, Chakole D and Mukkanti K developed stability-indicating UPLC method for desloratadine and its impurities in pharmaceutical dosage forms by using Waters Aquity BEH C18 column with mobile phase containing a gradient mixture of solvents A and B.The eluted compounds were monitored at 280nm.[8]
Ø  El-Enany N,El-Sherbiny D,Belal F developed Spectrophotometric, spectrofluorometric and HPLC determination of desloratadine in dosage forms and human plasma by using four methods. Methods I and II are based on coupling DSL with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.6 where a yellow colored reaction product was obtained and measured spectrophotometrically at 485 nm (Method I). The same product could be measured spectrofluorometrically at 538 nm after excitation at 480 nm (Method II). Methods III and IV, on the other hand, involved derivatization of DSL with 2,4-dinitrofluorobenzene (DNFB) in borate buffer of pH 9.0 producing a yellow colored product that absorbs maximally at 375 nm (Method III). The same derivative was determined after separation adopting HPLC (Method IV). The separation was performed on a column packed with cyanopropyl bonded stationary phase equilibrated with a mobile phase composed of acetonitrile-water (60 : 40, v/v) at a flow rate of 1.0 ml min(-1) with UV detection at 375 nm.[9]
Ø  El-Sherbiny DT, Nahed El-Enany, Belal FF, Hansen SH developed Simultaneous determination of loratadine and desloratadine in pharmaceutical preparations using liquid chromatography with a microemulsion as eluent by using cyanopropyl bonded stationary phase column, adopting UV detection at 247nm using a flow rate of 1ml/min. The optimized microemulsion mobile phase consisted of 0.1M sodium dodecyl sulphate, 1% octanol, 10%n-propanol and 0.3% triethylamine in 0.02M phosphoric acid, pH 3.0.[10]
OBJECTIVES OF THE STUDY:
Review of literature revealed that there is no stability indicating analytical method for Desloratidine in pharmaceutical dosage form.
Hence the objectives of the present work are:
Ø  To develop a HPLC method for estimation of Desloratidine.
Ø  To obtain the stress degraded products of Desloratidine by exposing a formulation which is under study for different stress conditions like acid, base, oxidative, reductive and neutral media.
Ø  To study the stress degradation behavior of Desloratidine by analyzing the different products obtained after degradation using HPLC method.
Ø  To validate the developed methods by ICH guidelines.
MATERIALS AND METHODS:
Materials
Desloratidine and Desloratidine Formulation, HPLC grade Water, Methanol, Ethanol, Acetonitrile, methylene chloride, octanol; 0.1N hydrochloric acid, dimethyl sulfoxide; pH 7.4 phosphate buffer; 0.1N sodium hydroxide.
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.
Ø  Journals
Indian Journal of Pharmaceutical Science
Journal of Pharmaceutical Science
Journal of Pharmacy Research
Open Medicine.
Scientia Pharmaceutica
Chemical and Pharmaceutical Bulletin
International Journal of Pharmaceutical Research
Journal of Pharmaceutical and Biomedical Analysis
International Journal of Pharmacy and Industrial Research
The Journal of Biological and Chemical Luminescence
Ø  Text Books and Pharmacopoeia
·  Sethi PD. HPLC: Quantitative Analysis of Drugs in Pharmaceutical Formulation. 3rd ed. Delhi: CBS Publisher and Distributors; 2008.
·  Bansal K. Chromatography. 1st ed. Delhi: Campus Books International; 2009.
·  Patania V.B. Analytical Chromatography. 1st ed. Delhi: Campus Books International; 2009.
·  Fong GW, Lam SK. HPLC in the Pharmaceutical Industry. 1st ed. New York: CBC Press; 2010.
·  Quanyun AXu, Lawrence AT. Stability-Indicating HPLC Methods for Drug Analysis. 3rd ed. Washington: American Pharmacists Association; 2008.
·  Swartz ME, Krull IS. Analytical Method Development and Validation. 1st ed. New York: Marcel Dekker, INC; 2009.
·  United States Pharmacopoeia-National Formulary. Published by IRAs; 2007.
·  Indian Pharmacopoeia, Government of India, Ministry of Health and Family Welfare, Published by The Indian Pharmacopoeia commission Gaziabad, 2; 2007.
Ø  Internet Browsing
·  www.sciencedirect.com
·  www.google.com
·  www.rxlist.com
·  www.medlineindia.com
·  www.google scolar.com
Method of Collection of Data (Including Sampling Procedures, If Any)
Ø  Procurement of drugs sample and marketed formulations.
Ø  Solubility determination of Desloratidine in various solvents and buffers.
Ø  Studying the spectra of the drug in UV–Visible region in different solvents/buffers and selecting the solvents for various analytical studies.
Ø  Development of HPLC method, optimization of the method for estimation of Desloratidine.
Ø  Development of stability indicating HPLC method, optimization of the method for estimation of Desloratidine.
Ø  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)  Bondili S, Reddy SP. Spectroscopic method for determination of Desloratadine in bulk and its tablet dosage forms. Int J Pharm Ind Res 2011; 1(2): 131-34.
[Available from http://www.ijpir.com/admin/fckeditor/_samples/php/article/99_12.E.Print%20 IJPIR_218_11.pdf]
2)  Alam Razib M, Md. Ullah A, Mohammad Azad AK, Sultana R, Yasmin H and Hasnat. Validation and Application of a Modified RP-HPLC Method for the Quantification of Desloratadine in Pharmaceutical Dosage Forms. J Pharm Sci. 2006; 5(1-2): 1-4.
[Available from http://banglajol.info/index.php/JPharma/article/view/219/215]
3)  http://en.wikipedia.org/wiki/desloratadine (access date Aug 27, 2011).
4)  http://www.drugs.com/mmx/desloratadine (access date Aug 27, 2011).
5)  Gajjela R, Yalavarthi RK, Vyas K, Mulukutla VS, Khagga M. A New Validated Liquid Chromatographic method for the determination of Loratadine and its Impurities. Sci Pharma. 2011; 79: 277-91.
[Available from http://www.scipharm.at/download.asp?id=952]
6)  Mallapu Rani E, Ahad HA, Sreenivasulu R, Rani M, Mandava G, Reddy B. KK, Kranthi G. Spectrophotometric determination of Desloratadine in pharmaceuticals by using difference spectrophotometric method. J Pharm Res. 2011; 4(3):730-31.
[ Available from http://jpronline.info/article/viewFile/6414/3267]
7)  Walash MI,F. Belal F,El-Enany N,Eid M,El-Shaheny RN. Stability-indicating micelle-enhanced spectrofluorimetric method for determination of loratadine and desloratadine in dosage forms. The Journal of Biological and Chem Lumin. 2011; 26(4).
[Available from http://www.ncbi.nlm.nih.gov/pubmed/21491578]
8)  Dantu DR, Satyanarayana NV, Reddy AM, Sait SS, Chakole D and Mukkanti K. Stability-indicating UPLC method for desloratadine and its impurities in pharmaceutical dosage forms. J Pharm Biomed Anal. 2011; 56(2):464.
[Available from http://www.sciencedirect.com/science/article/pii/S0731708509005470]
9)  El-Enany N,El-Sherbiny D,Belal F. Spectrophotometric, spectrofluorometric and HPLC determination of Desloratadine in dosage forms and human plasma.Chem Pharm Bull (Tokyo). 2007; 55(12):1662-70.
[Available from http://www.ncbi.nlm.nih.gov/pubmed/18057737]
10) El-Sherbiny DT, Nahed El-Enany, Belal FF, Hansen SH. Simultaneous determination of loratadine and desloratadine in pharmaceutical preparations using liquid chromatography with a microemulsion as eluent. J Pharm Biomed Anal. 2007; 43(4):1236-42.
[Available from http://www.sciencedirect.com/science/article/pii/S0731708506007205]
9. / Signature of the candidate / (PATEL AVINASHBHAI HASMUKHLAL)
10. / Remarks of the Guide / RECOMMENDED FOR THE DISSERTATION WORK.
11. / Name & Designation of
(in block letters)
11.1  Guide
11.2 Signature / Mrs. Ritu VIVEK Kimbahune,
ASSISTANT PROFESSOR,
DEPARTMENT OF QUALITY ASSURANCE,
NARGUND COLLEGE OF PHARMACY,
BANGALORE.
11.3  Co-Guide
11.4 Signature / R.V.V. SARMA,
MANAGER-AR & D,
V.B. MEDICARE PRIVATE LIMITED,
(SUBSIDIARY OF BIOPLUS LIFE SCIENCES)
HOSUR-635 109, TAMIL NADU.

12. / 11.5 Head of the department
11.6 Signature
12.1 Remarks of Principal
12.2 Signature / DR. J. N. NARENDRA SARATH CHANDRA
PROFESSOR, HEAD OF THE DEPARTMENT,
DEPARTMENT OF QUALITY ASSURANCE
NARGUND COLLEGE OF PHARMACY,
BANGALORE.
FORWARDED AND RECOMMENDED FOR FAVOURABLE CONSIDERATION.