“DESIGN AND CHARACTERISATION OF FAST DISSOLVING SUBLINGUAL FILMS OF MONTELUKAST SODIUM”

MASTER OF PHARMACY DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BANGALORE.

By

Miss. PRABHU SHRUTI CHANDRAKANT

M.PHARM – I

Under The Guidance of

Dr. A.R. SHABARAYA M. Pharm., Ph.D.

DEPARTMENT OF PHARMACEUTICS.

SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE – 574143

2012-2014

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the Candidate and Address: / MISS.PRABHU SHRUTI
CHANDRAKANT
1stYEAR M.PHARM,
DEPT. OF PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
2. / Name of the Institution: / SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, FARANGIPETE POST, MANGALORE-574143.
3. / Course of Study and Subject: / MASTER OF PHARMACY
INPHARMACEUTICS
4. / Date of Admission: / 26/5/2012
5. / Title of the Project:
“DESIGN AND CHARACTERISATION OF FAST DISSOLVING SUBLINGUAL FILMS OF MONTELUKAST SODIUM’’
6.
7.

8.
/ Brief Resume of the intended work:
6.1 Need of the study:
Recently there has been increased demand for novel dosage form to gain more patient compliance. Fast dissolving films recently have acquired great importance in pharmaceutical industry due to their unique properties and advantages.1
Fast dissolving film is a type of drug delivery system which when placed in oral cavity it rapidly disintegrates and dissolves to release the medication for oromucosal and intragastric absorption, without chewing and intake of water.1
Drug delivery via oral mucous membrane is considered to be a promising alternative to the oral route. The sublingual area(floor of the mouth) of the oral cavity is more permeable than the buccal (cheek) area which is in turn more permeable than the palatal area (roof of the mouth). New sublingual technologies address many pharmaceutical and patient needs, ranging from enhanced life cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia. Sublingual administration of drug means placement of drug under the tongue and drug reaches directly into the blood stream through the ventral surface of the tongue and floor of the mouth.
ADVANTAGES OF SUBLINGUAL FILMS
  1. Rapid onset of action can be achieved compared to the oral route.
  2. Drug is protected from degradation due pH and digestive enzymes.
  3. Improved patient compliance due to elimination of associated pain with injections, administration of drugs in unconscious patients, convenience of administration.
  4. Low dosage gives high efficacy and also reduces the risk of side effects.
  5. The large contact surface of oral cavity contributes to rapid and extensive drug absorption.
  6. Due to rapidity in action, these sublingual dosage forms are widely used in emergency conditions.
  7. Rapid absorption and higher blood levels due to high vascularisation of the region, therefore used particularly for administration of anti angina drugs.
  8. The use of mucoadhesive polymers in the films will enable them to adhere to the sublingual mucosa for better retention and drug absorption.2
MONTELUKAST SODIUM
Montelukast sodium is a leukotriene receptor antagonist (LTRA) used in maintenance treatment of asthma and to relieve symptoms of seasonal allergies. Montelukast blocks the action of leukotriene D4 on the cysteinylleukotriene receptorCysLT1 in lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction which is caused by leukotriene and results in less inflammation. Montelukast sodium has a half life of 2.5 to 5.5 hours. It is freely soluble in ethanol, methanol and water and practically insoluble in acetonitrile and its bioavailability is 63%.
The present aim is to formulate and characterise fast dissolving sublingual films of montelukast sodium for rapid dissolution of drug and absorption which may produce rapid onset of action in the treatment of asthma and seasonal allergies and also to improve the bioavailability of the drug.3
6.2 – Review of literature:
  1. BhupinderBet al1have prepared fast dissolving sublingual films of Rizatriptan Benzoate using combination of HPMC E15 and maltodextrin as polymer, sodium starch glycolate as disintegrating agent. The study concluded that all batches showed acceptable mechanical properties with invitro disintegration time of 30s. Formulation with 15 mg HPMC E15 and 5 and 10 mg of glycerol exhibited maximum drug release (90%) within in 6mins and permeation (71%) in 20mins.
  2. Narang N. et al2 highlighted the different sublingual dosage forms, factors affecting sublingual absorption, advantages, various in vitro and in vivo evaluation parameters and commercially available sub lingual dosage forms. It was studied that compared to oral dosage forms, sublingual absorption is generally much faster and more efficient.
  3. Ghorrwade V et al3 have prepared fast dissolving oral films of Montelukast sodium by using solvent casting method using HPMC as film base with different concentrations of super disintegrants like microcrystalline cellulose and crospovidone. And the study concluded that formulations with 4% crospovidone and 10% of MCC respectively shows maximum cumulative percentage drug release of 97.42% and 94.64% and were found to be the best formulations.
  4. Kolandet al4 prepared fast dissolving sublingual films of Ondansetron hydrochloride by using polyvinyl alcohol, polyvinyl pyrrolidone, carbopol 934P in different ratio by solvent casting method and using PEG 400 as plasticizer andmannitol and sodium saccharin as a sweetners and it was studied that use of water soluble sweeteners likemannitol not only enhanced the taste of Ondansetron Hydrochloride containing films but also increased the drug release (79.69%) and permeation (77.04%).
  5. Qadir Ket al5have prepared fast dissolving sublingual films of Loratadine by solvent casting method using polymers like HPMC, PVP and HPC in different ratios, and artificial sweetener Aspartame to mask the taste. The study concluded that all the formulations showed 70-92% release within 4mins by in vitromethod and 64-86% within 4mins during ex vivo drug release studies.
  6. Koland M et al6have prepared fast dissolving sublingual films of Ondansetron Hydrochloride by using polyvinyl alcohol, polyvinyl pyrrolidone, carbopol 934P in different ratios by solvent casting method. The study concluded that all formulations showed 81-88% release within 7mins by in vitro method and 67-70% within 40mins during ex vivo drug permeation studies.
  7. .and 67-70% within 40mins during ex vivo drug permeation studies.ethodse. international ies.ntage drug release of 97.42% and 94.Prasanthi N.L.et al7 have designed sublingual fast dissolving films for an antiasthmatic drug, Salbutamol sulphate by solvent casting method using different polymers HPMC, HPC and sodium alginate and aspartame as sweetener. The study concluded that films containing HPMC (2%), tween80 (0.5%w/w) and aspartame (0.5%w/w) showed optimum performance against all other prepared formulations.
  8. Kaza R. et al8 have designed fast dissolving oral films of Valsaran by solvent casting method using different grades of HPMC and propylene glycol as plasticizer. It was studied that the formulation containing HPMC and Valsartan solid dispersion with guar gum in the ratio 1:3 showed excellent film forming capacity along with disintegration time 42sec and percentage drug release 95% at 10 mins.
  9. Desu P. et al9 formulated fast dissolving oral films of an anti migraine Zolmitriptan using HPMC as film former and propylene glycol as plasticizer. It was studied that the formulation shows good mechanical properties and disintegration time within 1min and followed zero order kinetics No degradation of formulation was seen at high temperature and humidity conditions.
  10. Mishra R. et al10 formulated rapidly dissolving films of cetrizine hydrochloride using pullulan as film forming agent by solvent casting method. The in vitro and in vivo disintegration time of the optimised batch was found to be 30sec and 20sec respectively. The optimised batch was found to be stable for a period of six months at 25oC/40%RH.
  11. Singh S. et al11 formulated and evaluated fast dissolving oral film of Levocetrizine hydrochloride using sodium alginate as polymer by solvent casting method. It was studied that the formulation containing 2.5% of sodium starch glycolate was found to be the best with minimum disintegration time and showing sufficient drug release after 6mins.
  12. Patel N. K. et al12 highlighted advantages, disadvantages, different sublingual formulations and their evaluation.
  13. Kunte S. et al13have formulated and evaluated fast dissolving oral films of verapamil by solvent casting using HPMC E6 and maltodextrin. The disintegration time was found to be 20.4 to 28.6 secs and it was studied that formulation containing 2% HPMC E6 and 3.5% maltodextrin showed optimum performance against other formulations.
  14. Raju S. et al14 have formulated and evaluated oral films of Metoclopramide hydrochloride for paediatric use by solvent casting using HPMC and carboxy methyl cellulose. It was studied that formulation containing 10.33% of HPMC E6 released 90.40% of drug within 30sec and was considered the best formulation.
  15. Shelke PV et al15have formulated and evaluated rapidly disintegrating film of Amlodipinebesylate by solvent casting using sodium alginate as polymer and aspartame as sweetener. It was studied that all films have smooth surface and good folding endurance, and drug content of all the films was found to be 4.6 to 5.01mg.
6.3 – Objectives of the study:
The present study is planned with the following objectives:
  1. To characterize the formulation with respect to drug-excipient interaction studies (FTIR).
  2. To prepare the fast dissolving sublingual films of Montelukast sodium by solvent casting method.
  3. To evaluate the formulations with respect to various physical parameters (Physical appearance, surface texture, thickness of film, swelling index, moisture uptake, folding eudurance, surface pH), in vitro studies
(Disintegration and dissolution).
  1. To carry out comparative studies between best formulation and a marketed Montelukast sodium tablet.
  2. To carry out stability studies as per ICH guidelines.

Materials and Methods:

Materials:
a)Drug : Montelukast sodium
b)Polymers : Natural polymers
Pullulan, starch, sodium alginate, maltodextrins, etc
Synthetic polymers
Hydroxyl propyl methyl cellulose, sodium carboxy
Methyl cellulose, etc
c)Plasticizers :Polyethylene glycol, glycerol, etc.
d)Superdisintegrants : Crospovidone, micro crystalline cellulose (MCC),
Sodium starch glycolate,etc
Methods:
Sublingual films of Montelukast sodium areprepared by Solvent casting method.
7.1 Source of data:
Review of literature from
a)Journals such as
  • International Journal of Research in Pharmaceutical and Biomedical Sciences
  • International Journal of Pharmacy and Pharmaceutical Sciences
  • International research journal of pharmacy
  • International journal of chemical sciences
  • International journal of drug development and research
  • Scholars research library
  • World journal of medical pharmaceutical and biological sciences
  • Indian journal of pharmaceutical education and research
  • International journal of innovative pharmaceutical research
b)Internet browsing
c)Laboratory based studies
7.2 – Methods of collection of data:
  • An overview of Montelukast sodium sublingual films.
  • Formulation of sublingual films of Montelukast sodium.
  • Evaluation of formulated Montelukast sodium sublingual films.
  1. Drug excepient interaction studies.
  2. Physical appearance & surface texture
  3. Thickness of the film
  4. Swelling index
  5. Moisture uptake
  6. Folding endurance
  7. Surface pH
  8. Tensile strength measurement
  9. Uniformity of drug content
  10. Disintegration test
  11. In vitro dissolution studies
  12. Ex vivomucoadhesion time and drug release
  13. Stability studies as per ICH
  • Drug and excipients interaction:
By FTIR Spectroscopy
  • In vitro drug release:
By dissolution studies
7.3 Does the study require any investigations or interventions to beconducted on patients or other humans or animals? If so, please describe briefly.
-Not applicable
7.4Has ethical clearance been obtained from your institution in case of 7.3?
- Not applicable
List of references:
  1. Bhyanbhupinder, Jangrasarita. Formulation and evaluation of fast dissolving sublingual films of Rizatryptan Benzoate. Int J Drug Dev & Res.2012;4(1):133-43
  2. Narang N, Sharma S. Sublingual mucosa as a route for systemic drug delivery. Ind J PharmPharm Sci.2011;3(2):18-22.
  3. Ghorwade V, Patil A, Patil S, Srikonda K, Kotagiri R, Patel P. Development and evaluation of fast dissolving film of Montelukast sodium. World J Med Pharm & Bio Sci.2011;1(1):06-12
  4. Koland M, Sandeep VP, Charyulu NR. Fast Dissolving Sublingual Films of Ondansetron hydrochloride: Effect of additives on invitro drug release and mucosal permeation. JYoung Pharm.2010; 2(3):216-22.
  5. Qadir K, Charyulu RN, Prabhu P, Bhatt S, Shastry CS. Formulation and evaluation of fast dissolving films of Loratidine for sublingual use. Int Res J Pharm.2012;3(7).
  6. Koland M, Sandeep VP, Charyulu N, Subrahmanyam EVS. The design and characterization of sublingual films of Ondansetron Hydrochloride. IntJ Chem Sci.2009;7(4):2927-938.
  7. Prasanthi NL, Krishna S.C., Gupta E.M., Manikiran S.S., Rao R.N. Design and development of sublingual fast dissolving films for an anti asthmatic drug. Sch Res Lib.2011;3(1):382-95.
  8. Kaza R, Kumar A.R. Design and charactisation of fast dissolving films of Valsartan. Int J InnoPharm Res.2012;3(2):212-19
  9. Desu P, Sahu M. Formulation and evaluation of fast dissolving films of Zolmitriptan. Int Res J Pharm.2012;3(5):373-76.
  10. Mishra R, Amin A. Formulation and characterisation of rapidly dissolving films of Cetrizine hydrochloride using pullulan as film forming agent. Ind J PharmEdu & Res.2011;45(1):71-77
  11. Singh S, Gangwar S, Garg G, Garg V, Sharma PK. Formulation and evaluation of rapidly disintegrating film of Levocetrizine hydrochloride. Sch Res Lib.2(2):434-39
  12. Patel N.K., Pancholi SS. An overview on: Sublingual route for systemic drug delivery. Int J Res Pharm Biomed Sci.2012;3(2):913-23
  13. Kunte S, Tandale P. Fast dissolving strips: A novel approach for the delivery of verapamil. J PharmBioallied Sci.2010;2(4):325–28.
  14. Raju S, Reddy S.P., Kumar A.V., Deepthi A, Reddy S.K, Reddy MVP. Flash release oral films of Metoclopramide hydrochloride for paediatric use: Formulation and in vitro evaluation. J ChemPharm Res.2011;3(4):636-46.
  15. Shelke PV, Dumbare AS, Gadhave MV, Jadhav SL, Sonawane AA, Gaikwad DD. Formulation and evaluation of rapidly disintegrating film of Amlodipinebesylate. J Drug Del & Thr.2012;2(2):72-75

9. / Signature of the candidate / (PRABHU SHRUTI CHANDRAKANT)
10. / Remarks of the Guide / The work, which is assigned to
Miss PRABHU SHRUTI CHANDRAKANTis under my guidance.
11. / 11.1 Name and Designation of the
Guide / Dr.A.R. SHABARAYA M.Pharm., Ph.D.
HOD and Principal.
Department of Pharmaceutics
Srinivas College of Pharmacy
Valachil, Mangalore- 574143
11.2 Signature / (Dr. A. R. SHABARAYA)
11.3 Name and Designation of the
Co-Guide / ------
11.4 Signature / ------
11.5 Head of the Department / Dr. A. R. SHABARAYA M.Pharm.,Ph.D.
Principal and Director,
Department of Pharmaceutics,
SrinivasCollege of Pharmacy,
Valachil, Mangalore- 574143
11.6 Signature / (Dr. A. R. SHABARAYA)
12. / 12.1 Remarks of the Principal / Recommended and forwarded for favourable consideration.
12.2 Signature / (Dr. A. R. SHABARAYA)