Rajiv Gandhi University of Health Sciences, Karnataka Bangalore s8

FORMULATION AND EVALUATION OF ORAL FAST DISSOLVING FILM OF LEVOCETIRIZINE

M. Pharm. Dissertation Protocol Submitted to the Rajiv Gandhi University of Health Sciences, Karnataka Bangalore.

PATEL RIZWAN HASHAM B. Pharm.

UNDER THE GUIDANCE OF M. A. SALEEM M.PHARM (Ph.D) Professor PG Dept. of Pharmaceutics

DEPARTMENT OF PHARMACEUTICS LUQMAN COLLEGE OF PHARMACY, GULBARGA 2011-12 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA BANGALORE

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. Name of the Candidate and PATEL RIZWAN HASHAM Address (In block letters) C/O LUQMAN COLLEGE OF PHARMACY, P.O BOX NO. 86, BEHIND P&T COLONY, OLD JEWARGI ROAD, GULBARGA 585102. 2. Name of the Institution LUQMAN COLLEGE OF PHARMACY

3. Course of Study and Subject M.PHARM. (PHARMACEUTICS)

4. Date of Admission to Course 04TH JUNE 2011

5. Title of the Topic FORMULATION AND EVALUATION OF ORAL FAST DISSOLVING FILM OF LEVOCETIRIZINE

6. BRIEF RESUME OF THE INTENDED WORK

6.1 Need for the study:

Recent developments in the technology have presented viable dosage alternatives from oral route for pediatrics, geriatric, bedridden, nauseous or noncompliant patients. Mouth dissolving films, a new drug delivery system for the oral delivery of the drugs, was developed based on the technology of the transdermal patch. The delivery system consists of a very thin oral strip, which is simply placed on the patient’s tongue or any oral mucosal tissue, instantly wet by saliva thereby the film rapidly hydrates and adheres on to the site of application. It then rapidly disintegrates and dissolves to release the medication for oromucosal absorption. Fast dissolving oral films have several advantages over the conventional dosage forms. So they are of great importance during the emergency cases such as allergic reactions and asthmatic attacks, whenever immediate onset of action is desired. Pharmaceutical companies and consumers alike have embraced oral thin films (OTFs) as a practical and accepted alternative to traditional OTC medicine forms such as liquids, tablets, and capsules. Oral thin films offer fast, accurate dosing in a safe, efficacious format that is convenient and portable, without the need for water or measuring devices1.Some of the drugs like salbutamol2, mountelukast3, verapamil4, triclosan5 etc. reported as mouth dissolving films. Some of the pharmaceutical companies prepared and marketed mouth dissolving films of drug like benzocaine films, caffeine films (Dow chemical company), Doneprezil rapid dissolving films, ondensetron rapid dissolving film (Labtec Pharma).1Allergenic rhinitis (AR) is estimated to affect 10-30% of adults and up to 40% of children in the USA, making it the sixth most common chronic illness. This disease commonly develops before the age of 20 years, with its prevalence increasing throughout childhood and peaking during adolescence. Common symptoms include sneezing, rhinorrhea, itchy nose , palate and/ or throat, itchy, watery eyes, and nasal decongestion. In the past few decades lots of work have been done on oral fast dissolving for the management of allergenic rhinitis. In the present scenario to treat allergenic rhinitis oral fast dissolving films has been introduced.6

Levocetirizine is a class of second generation antihistaminic agent. It is the active enantiomer of cetirizine, its principal effects are mediated via selective inhibition of H1 receptor.It dose not prevent actual release of the histamine from the mast cells, but prevents its binding to its receptor. The daily dose of levocetirizine is 10mg per day. It is rapidly absorbed in internal administration, the simultaneous use of meal decreases the absorption rate but does not influence over its completeness. Levocetirizine bioavailability is 100%.The binding with plasma proteins is 90%. The period of half-life is 7–10 hours.7,8

Hence in the present work an attempt will be made to prepare and evaluate oral fast dissolving film of levocetirizine for the effective management of allergenic rhinitis. 6.2 Review of Literature: Literature survey was carried out on the proposed research work by referring various

Scientific Research Journals, Internet, Helinet facilities and science direct.

Lawrence M et al, reviewed Pharmacoeconomics of levocetirizine in allergic rhinitis and chronic idiopathic urticaria: concideration for the USA. Arya A et al, concluded that fast dissolving oral films have several advantages over the conventional dosage forms. So they are of great importance during the emergency cases such as allergic reactions and asthmatic attacks whenever immediate onset of action is desired. Prashanti N L et al, studied and concluded that the fast dissolving films could be formulated with the easily available components such as HPMC, HPC and Sodium Alginate. Salbutamol sulphate, a highly water soluble and bitter drug could be successfully incorporated in the fast dissolving films with the help of solubilizers such as Tween 80 and the bitter taste of the drug could successfully be masked by the use of aspartame in the films. Vijaykumar G et al, concluded that, fast dissolving films of montelukast sodium can be prepared by solvent casting technique using gelatin as film base and crosspovidone and MCC as superdisintegrants. Kunte S et al, formulated and Evaluated that fast dissolving strips of verapamil can be made by solvent casting technique with enhanced dissolution rate, masking and hence better patient compliance and effective therapy. Dinge A et al, studied that the fast dissolving films could be formulated with the easily available components such as HPMC and xanthan gum.Triclosan ,a poorly water soluble and bitter drug could be successfully incorporated in the fast dissolving film with the help of solublizers such as poloxamer 407. Gandhi G.S et al, studied that levocetirizine orodispersible tablet prepared using different types and concentrations of superdisintegrant by direct compression method which was confirmed by various charecterisation and evaluation studies. Chaudhary D.R et al, concluded that the combination of methocel E15 and PEG 400 exhibited excellent mechanism properties (tensile strength 6.32 N/mm2), drug content(98.35%) and dissolution characteristic (DT 47 sec). the research work done here suggested that the exciting possibility of levocetirizine as fast dissolving film.

6.3 Objectives of the study: Fast dissolving films of levocetirizine will be prepared to provide fast action in allergenic rhinitis with the following objectives 1 To prepare the cyclodextrin complex of levocetirizine and evaluated by DSC and IR. 2 To prepare the films by hydrophilic polymers and cyclodextrin by solvent casting method. 3 To evaluate the oral film for surface pH, mechanical strength, thickness, folding endurance, tensile strength. 4 To study the in vitro release.

7. MATERIALS AND METHODS: 7.1Material and Source: Drug : Levocetirizine Polymers : Hydrophilic/ natural/synthetic Cyclodextrin and superdisintegrants. All other chemical & ingradients used will be of analytical grades.

Equipments: UV/Visible spectrophotometer 1700 (Shimadzu) IR- spectrophotometer- JASCO FT/IR 5300 Single pan electronic balance (Dhona equipment Pvt ltd Kolkata) Digital balance (shimadu corporation BL-2204) Digital type ph meter (elico LT – 122) Electrolab dissolution apparatus (USPXXIII) Tensiometer etc.

7.2 Method: 1. UV/ visible spectroscopic estimation of levocetirizine. 2. Preparation of drug cyclodextrin complex by kneading method. 3. Evaluation of cyclodextrin complexes with FTIR and DSC. 4. preparation of drug cyclodextrin loaded oral films by solvent casting method. 5. Evaluation of oral films for surface pH, folding endurance, in vitro disintegration time, thickness of the film, swelling index.

7.3 Does the study require any investigation or intervention 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 NO 8. LIST OF REFERENCES:

1. Arya A, Chandra A, Sharma V, Pathak K. “Fast Dissolving Oral Films: An Innovative Drug Delivery System And Dosage Form.A review Int. J. ChemTech Res. 2010;2(1):576-583.

2. Prasanthi N L, Krishna C S, Gupta M.E, Manikiran S.S, Rao N.R. “Design and Development of Sublingual Fast Dissolving Films for and Antiasthmatic Drug”. Der Pharmacia Lettre.2011;3(1): 382-395.

3. Ghorwade V, Patil A, Patil S, Ikkurthy K, Inuganti S K, Porandla V. “ Formulation And Evaluation Of Montelukast Fast Dissolving Film By Using Gelatin As A Film Base”. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2011;2(3):888

4. Kunte S, Tandale P. “Fast Dissolving Strips: A Novel approach For The Delivery Of Verapamil”. Journal of pharmacy and bioallied sciences.2010;2(4):325-328. . 5. Dinge A, Nagarsenker M. “Formulation and Evaluation Of Fast Dissolving Films For Delivery Of Triclosan To The Oral Cavity”. AAPS PharmSciTech.2008;2(9)349-356.

6. Dubuske M L, Seal B, Brown C J M X. “Pharmacoeconomics of Levocetirizine In Allergic Rhinitis And Chronic Idiopathic Urticaria: Considerations For The USA . Expert rev. Pharmacoeconomics outcome Res. 2008;8(3):233-241.

7. Gandhi G S, Mundhada D R , Bhaskaran S. “Levocetirizine Orodispersible By Direct Compression Method”. J. of Applied Pharm.Sciences.2011;5(1):145-150.

8. Choudhary D R, Patel V A, Chhalotiya U K, Patel H V, Kundawala A J. “Formulation And Evaluation Of Fast Dissolving Film Of Levocetirizine Dihydrochloride Using Different Grades Of Methocel”. J. of Pharmacy Res.2011;9(4):2919-2924

9. Murata Y, Isobe T, Kofuji K, Nishida N, Kamaguchi R. “Preparation Of Fast Dissolving Films for Oral Dosage From Natural Polysaccharides”. MDPI.2010;3(8):4291-4299.

10. Koland M, Sandeep VP, Charyulu NR. “Fast Dissolving Film of Ondansetron Hydrochloride:Effect of Additives on In vitro Drug Release And Mucosal Permeation”. J. of Young Pharmacist.2010;2(3):216-222.

11. Shimoda H,Taniguchi K, Nishimra M, Matsurra K, Tsukioka T, Yamashita H, Inagaki N, Hirano K, Yamamoto M, Kinosada Y, Itoh Y. “Preapration of a Fast Dissolving Oral Thin Film Containing Dexamethasone:A Possible Application To Antiemesis During Cancer Chemotherapy”. Europiean Journal of Pharmaceutics and Biopharmaceutics.2009;73:361-365. 12. Nishimura M, Matsuura K, Tsukioka T, Yamashita H, Inagaki N, Sugiyama T, Itoh Y. “In Vitro and In Vivo Characterstics of Prochlorperazine Oral Disintegrating Film”. Int. J. Pharmaceutics.2008;368:98-102.

13. Saini S, Nanda A, Hooda M, Komal, Dhari J. “Formulation and Evaluation of Mouth Dissolving anti-Allergic Tablet of Levocetirizine Dihydrochloride”. J. Chem. Pharm. Res.2011;3(5):450-455.

14. Prabhu P, Malli R, Koland M, Vijaynarayana K, D’Souza U, N.M Harish, Shastry CS, Charyulu R.N. “Formulation and Evaluation of Fast Dissolving Film of Levocetirizine Di Hydrochloride”. Int J. of Pharmceutical investigation.2011;1(2):99-104.

15. Saini S, Nanda A, Dhuri J. “Formulation, Development And Evaluation Of Oral Fast Dissolving Anti-Allergic Film Of Levocetrizine Dihydrochloride”. J. Pharm. Sci. Res. 2011;3(7):1322-1325.

16. Sreekanth J, Lakshmi P K. “Formulation And Evaluation Of Fast Dissolving Oral Thin Film Of Levocetirizine Hydrochloriode With Eudragit Epo And Optimisation Through Taguchi Orthogonal Experimental Design”. Int. Journal of Pharm. Sciences of review and Research.2011;11(1):115-123. 9. Signature of Candidate

[PATEL RIZWAN HASHAM] 10. Remarks of the Guide Development of fast dissolving oral films is a novel concept for the rapid and effective management of diseases. Hence recommended for registration.

11. Name & Designation of (in block letters) 11.1 Guide M.A.SALEEM M.PHARM.(PH.D) PROF. DEPT.OF PHARMACEUTICS, LUQMAN COLLEGE OF PHARMACY, P & T COLONY, JEWARGI ROAD, GULBARGA. 11.2 Signature

11.3 Co-Guide

11.4 Signature

12. 12.1 Remarks of the We will provide all necessary facilities required for Chairman & Principal the proposed research work.

So, recommended for registration.

12.2 Signature