“FORMULATION AND EVALUATION OF FAST DISSOLVING FILMS OF

β – BLOCKERS”

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BENGALURU, KARNATAKA.

BY

SYED MAHABOOB.

M.PHARM, PART- I.

DEPARTMENT OF PHARMACEUTICS.

UNDER THE GUIDANCE OF

Dr.N.S.CHANDRA SHEKAR, M.PHARM, Ph.D,

PROFESSOR

DEPARTMENT OF PHARMACEUTICS.

Vivekananda College of Pharmacy,

Dr.Rajkumar Road, RajajinagarІІ Stage,

Bengaluru (Dist)-560055.

2010

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BENGALURU.

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the candidate andaddress:- /

SYED MAHABOOB.

DEPARTMENT OF pharmaceutics,
VIVEKANANDA COLLEGE OF PHARMACY, dR.RAJKUMAR ROAD,
RAJAJINAGAR ІІ STAGE,
BENGALURU(DIST) - 560055,
KARNATAKA.
2. /

Name of the institution:-

/ VIVEKANAnDA COLLEGE OF PHARMACY, DR.RAJKUMAR ROAD,
RAJAJINAGAR ІІ STAGE,
BENGALURU(DIST) - 560055,
KARNATAKA.
3. /

Course of study & subject:-

/ MASTER OF PHARMACY IN pharmaceutics.
4. /

Date of admission to course:-

/ 29th NOVEMBER2010
5. /

Title of the topic:-

“FORMULATION AND EVALUATION OF FAST DISSOLVING FILMS OF β - BLOCKERS”
6. /
Brief resume of the intended work:
6.1 Need for the study:
Fast-dissolving drug-delivery systems were first developed in the late 1970s as an alternative to tablets, capsules, and syrups for pediatric and geriatric patients who experience difficulties swallowing traditional oral solid dosage forms. In response to this need, a variety of orally disintegrating tablet (ODT) formats were commercialized. Amongst other factors, palatability of formulations of pediatric oral medications is one therapeutic regimens1,2. Most ODT products were formulated to dissolve in less than one minute when exposed to saliva to form a solution that could then be more easily swallowed. Dissolvable oral thin films (OTFs) evolved over the past few years from the confection and oral care markets in the form of breath strips and became a novel and widely accepted form by consumers for delivering vitamins and personal care products.
Recent developments in the technology have presented viable dosage alternatives from oral route forpediatrics, geriatric, bedridden, nauseous or noncompliantpatients. Buccal drug delivery has latelybecome an important route of drug administration.Various bioadhesive mucosal dosage forms have been developed, which includes adhesive tablets, gels, ointments, patches and more recently the use of polymeric films for buccal delivery, also known asmouth dissolving films3.
Basically the (ODF) can be considered as an ultrathin strip of postage stamp size with an active agent or active pharmaceutical ingredient and other excipients. The advantages of convenience of dosing and portability of ODF have led to wideracceptability of this dosage form by pediatric as well as geriatricpopulation equally4.
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 the film rapidly hydrates and adheres onto the site of application. It then rapidly disintegrates and dissolves to release the medication for oromucosal absorption or with formula modifications, will maintain the quick-dissolving aspects allow for gastrointestinal absorption to be achieved when swallowed. In contrast to other existing, rapid dissolving dosage forms, which consist of liophylisates, the rapid films can be produced with a manufacturing process that is competitive with the manufacturing costs of conventional tablets5.
Pharmaceutical companies and consumers alike have embraced OTFs as a practical and accepted alternative to traditional OTC medicine forms such as liquid,tablets, and capsules. OTFs offer fast, accurate dosing in a safe, efficacious format that is convenient and portable, without the need for water or measuring devices6. OTFs are typically the size of a postage stamp and disintegrate on a patient's tongue in a matter of seconds for the rapid release of one or more APIs7(Active pharmaceutical ingrediants).
Special features of mouth dissolving films:8
• Thin elegant film
• Available in various size and shapes
• Unobstructive
• Excellent mucoadhesion
• Fast disintegration
• Rapid release
The advantages of fast dissolving films:
  1. Availability of larger surface area that leads to rapiddisintegrating and dissolution in the oral cavity.
  1. The oral fast dissolving films are more flexible and they are easy of transportation and during consumer handling and storage.
  1. As compared to drops or syrup formulations, precision in theadministered dose is ensured from each of the strips.
  1. No need of water has led to better acceptability amongst thedysphagic patients. The difficulty encountered in swallowingtablets or capsules is circumvented. The dosage form can be consumedat anyplace and anytime as per convenience of the individual.
  1. The oral or buccal mucosa being highly vascularized, drugs canbe absorbed directly and can enter the systemic circulationwithout undergoing first‐pass hepatic metabolism. Thisadvantage can be exploited in preparing products withimproved oral bioavailability of molecules that undergo first pass effect9.
  1. Since the first pass effect can be avoided, there can bereduction in the dose which can lead to reduction in side effectsassociated with the molecule.
  1. Patients suffering from dysphagia, repeated emesis, motionsickness, and mental disorders prefer this dosage form as theyare unable to swallow large quantity of water.
  1. Enhanced stability.
  1. No risk of chocking.

6.2 Review of Literature:
7. /
  1. Bazigha K Abdul Rasool,et.al.had done the in vitro evaluation of micanozole mucoadhesive buccal films by solvent casting method use of Chitosan polymer. Propylene glycol and polyethylene glycol 3% w/w, tween 6% w/w, oleic 5% w/w as solubilizers. He done the various evaluations and he concluded that the muco adhesive buccal films for topical delivery of micanazole nitrate could be a successful mean for management of oral candidiasis10.
  1. Aditya Dinge and Mangal Nagaresenkar done formulation and evaluation of fast dissolving films for delivery of triclosan to oral cavity by useing HPMC and POLOXAMER as polymer and solubiliser. They concluded that the films prepared by the water soluble polymers could be successfully incorporated in the fast dissolving films with help of solubilizer such as polaxamere 407 and the bitter taste of the TC could be successfully masked by use of polaxamere 407 and eugenol in the film11.
  1. Kunte.S and Tandale.P prepared ODFS of verapamil by solvent casting technique usingHPMC and malodextrin as polymers. Films were found to be have uniform drug content evaluated and the values were found to be between 99.36% and 100.18% for different batches12.
  1. Basani Gavaskar, Subash Vijaya Kumar, studied the overview on fast dissolving films to compile the recent advancements and literatures regarding the fast dissolving films and they concluded that the many of the pharmaceutical companies are switching their product franchise from ODTs to ODFTs. This technology option can also provide a good platform for patent non-infringing product development13.
  1. Kulkarni Parthasarathi Kesavarao, Dixit take the fast dissolving films of rofecoxib by solvent casting method by use of HPMC as polymer. They concluded that mouth dissolving films containing rofecoxib 4%w/v of PVA film exibhited requive tensile strength, folding endurance, and percentage elongation14.
  1. Dr.Choudhary, Patel V.A are prepared the formulation and evaluation of quick dissolving film of levo cetrizine di hydro chloride by solvent casting method using HPMC and HPC as polymers. They concluded that films prepared with HPMC, HPC, CMC were transparent with smooth surface acceptable mechanical properties. There are no drug interaction with polymers, films disintegrated in 20 secs and dissolved in 55 secs drug release was found to be 80% in 120 secs15.
  1. Rakesh Patel Naik carried out the experiment on mouth melting film of ondansetran by use of HMC was polymer in solvent casting method.They found that optimization formulation passed entire evaluation test and scores better convenience than markted products .These suitable for pediatric and elderly patient due to its convenience16.
  1. Kulkarni, Deokule H.A are done the exploration of different polymers using the formulation of oral films by solvent casting method.They concluded that among all the polymers pullulan and HPMC E15 were showed desired film forming capacity,so pullulan is best film forming agent17.
Brief notes on Beta-Blockers:
These are also called as beta-adrenergic blocking agents are class of drugs used for various indications, but particularly for management of cardiac arrhythmias , myocardial infraction18 and hypertension19.
Beta- blockers blocks the action of endogenouscatecholamine and nor epinephrine (noradrenaline) on β-adrenergic receptors, part of sympathetic nervous system which mediates the fight or flight” response20,21. The fast dissolving films of β-blockers help to convenience of dosing and portability of ODF have led to wider acceptability of this dosage form by pediatric and geriatric patients.
Types of Receptors:
  1. β1-receptors- Act mainly in Heart and Kidney22.
  1. β2-receptors- Act on Lungs and GIT23.
  1. β3-receptors- Act on Fat cells.
DOSE:
For example Atenolol:
ADULT: 25-50mg once daily may increase to 100mg per day.
IV: 1-10ml l6-12hr.
6.3 Objective of the study:
The present work is an attempt:
  1. To develop Fast dissolving Films contains β- blockers.
  1. To evaluate for the characteristics like tensile strength, elastic modulus, Folding endusarance, swelling property, contact angle, in vitro disintegration time, in vitro dissolution studies, etc.
  1. To carry out in vitro dissolution studies of the film formulation.
  1. To carry out stability studies as per ICH guidelines.
MATERIALS AND METHODS:
7.1 MATERIALS:
1.Drug:β – blockers
2.Polymer: Analytical Graded polymers
3.Plasticizers
4.Sweetners
7.2) SOURCE OF DATA:
The preliminary data required for the experimental study is obtained from-.
1. CD-Rom search available at National Center for Scientific Information (NCSI), Indian institute ofSciences (IISc), Bangalore.
2. Journals,
3. Analytical chemistry Books ,
4. Library,
5. Relevant Books,
6. Internet Sources ,
7. Scientific abstracts.
7.3) METHODS:
  1. The fast dissolving films can be prepared by Solvent casting technique.
7.4)Does the study require any investigation to be conducted on patients/Humans/animals? If so, pleasedescribe briefly.
NO
7.5)Has ethical clearance been obtained from your institution in case of7.3
“NOT APPLICABLE”
8. REFERENCE
  1. Crama A, Breitkreutzb J, Desset‐Brèthesc S, Nunnd T and Tuleuf C, Challenges of developing palatable oral pediatric formulations, Int J Pharm, 2009;1(3):365-371.
  1. Florence A.T, Neglected diseases, neglected technologies, neglected patients? Int J Pharm. 2008; 1.Malke M, Shidhaye S, Kadam VJ. , Formulation and evaluation of Oxacarbazine fast dissolve tablets. Ind J Pharm Sci.2007;6(9): 211-221.
  1. Malke M, Shidhaye S, Kadam VJ. , Formulation and evaluation of Oxacarbazine fast dissolve tablets. Ind J Pharm Sci. 2007;6(9):211-214.
  1. Committee for Medicinal Products for Human Use, Reflection paper: formulation ofchoice for the pediatric population,2006;3(7):64-69.
  1. Suresh B, Halloran D, James L. Quick dissolving films: A novel approach to drug delivery.Drug.dev.tech, 2006;1(2):84-89.
  1. Frey.Film Strips and Pharmaceuticals, Pharma Mfg & Packag Sourcer,2006:92–93.
  1. Vondrak B, Barnhart, Scott. Dissolvable Films: Dissolvable Films for Flex Product Format in Drug Delivery.Pharmatech, 2008:1-5.
  1. Mashru R.C, Sutariya B.C, Parikh P.P. Development and evaluation of fast dissolving films of salbutamolsulphate.Drug Dev Ind Pharm,2005;31:25-34.
  1. Zhang H, Zhang J and Streisand J.B, oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications, Clin. Pharmacokinet.2002; 4(1): 661‐680.
  1. Bazigha K Abdul Rasool and Saeed A.Khan, in vitro evaluation of micanazole mucoadhesive buccal films by solvent casting,Int.J.Appld.pharmaceutics,2010; 2 (4):224-230.
  1. Adithtya Dinge and mangl nagaresenker, formulation and evaluation of fast dissolving film for delivery of triclosan to oral cavity by solvent casting, pharma sci Tech,2008;9(2):349-356.
  1. Kunte.S and Tandale.P, Fast dissolving films: A noval approach for the delivery of verapamil by solvent casting method, Indian J.pharm sci, 2010;8.287-293.
  1. Basani gavaskar, Subash vijaya kumar. Overview on fast dissolving films, Int.J.Pharm,pharmaceutical.sci,2010;1( 2), suppl 3.
  1. Kulkarni parthasarathi kesavarao and Dixit, fast dissolving films of rofecoxib by solvent casting method, Indian J.pharm sci, res v2009;9(2).175-182.
  1. Dr.choudhary and v.a.patel, formulation and evaluation of quick dissolving film of levo cetrizine dihydrochloride by solvent casting method, Indian.Pharm.sci,2009:3-9.
  1. Rakesh patel and naik shardul.., formulation devoloment and evaluation of mouth melting film of ondansetron by solvent casting method.Arch pharma and res, 2009;10(2):212-217.
  1. kulakarni A.S and Deokule H.A, Exploration of different polymers for use in the formulation of oral fast dissolving films by solvent casting method, J.current pharm res,2010; 2(1):33-35.
  1. Freemantle N, Cleland J, Young P, Mason J, Harrison J (June 1999). "beta Blockade after myocardial infarction: systematic review and meta regression analysis"2010;1730–1737.
  1. Cruickshank JM (August 2010). "Beta blockers in hypertension". Lancet376(9739): 415; author reply 415–416.
  1. Frishman.W.H.; Cheng-Lai. A, Nawarskas. JCurrent Cardiovascular Drugs2005:152-153.
  1. Arcangelo V.P.; Peterson A.M.Pharmacotherapeutics for advanced practice: a practical approach. Lippincott Williams & Wilkins.2006:205. 07.
  1. Frishman W.H.; Cheng-Lai A, Nawarskas J.Current Cardiovascular Drugs. 2009:153-155.
  1. Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD (August 1995). "Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity". The New England Journal of Medicine333 (6): 352–354.

Signature of candidate:

Remark of the guides:

/ The above given information is true and this work will be done under my guidance.
Name & Designation of
(in block letters)
11.1 Guide / Dr. N.S.CHANDRA SHEKAR,M.PHARM, Ph.D.
PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
VIVEKNANDA COLLEGE OF PHARMACY
DR.RAJKUMAR ROAD,
RAJAJINAGAR ІІ STAGE,
BENGALURU (DIST)-560055.
KARNATAKA.
11.2 Signature:
11.3 Co-guide (if any):
11.4 Signature:
11.5 Head of the Department / Mr. N.S.CHANDRA SHEKAR, M.PHARM, Ph.D. PROFESSOR
DEPARTMENT OF PHARMACEUTICS
VIVEKANANDA COLLEGE OF PHARMACY
DR.RAJKUMAR ROAD,
RAJAJINAGAR ІІ STAGE,
BENGALURU (DIST)-560055.
KARNATAKA.
11.6 Signature:
12.1Remarks of the Chairman & Principal: / The above-mentioned information is correct and I recommend the same for approval.
12.2 Signature:

From

SYED MAHABOOB.

M.Pharm, PART I

Dept.Pharmaceutics,

VivekanandaCollege of Pharmacy,

Dr.Rajkumar Road, Rajajinagar ІІ Stage.

Bengaluru (Rural)-560055.

TO

The Registrar (Evaluation),

Rajiv Gandhi Universityof Health Sciences,

Karnataka Bangalore,

4th ‘‘T’’ Block, Jaynagar,

Bangalore-560 041

(Through Proper Channel)

Sub: Submission of Synopsis of Dissertation

Respected Sir,

Herewith, I am submitting synopsis of dissertation work “FAST DISSOLVING FILMS OF β BLOCKERS” for registration in M.Pharm (Pharmaceutics) of Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka.

Kindly accept the same and acknowledge.

Thanking you,

Yours Faithfully,

(SYED MAHABOOB.)

Place: Bengaluru.

Date:

Guide:

Dr. N.S.CHANDRA SHEKAR M.Pharm,Ph.D,

PROFESSOR

DEPT OF PHARMACEUTICS, PRINCIPAL

Vivekananda College of Pharmacy, Vivekananda College of Pharmacy,

Dr.rajkumar Road, Rajainagar ІІ Stage, Dr.rajkumar Road, rajajinagar ІІ Stage,

Bengaluru (Dist)-560055. Bengaluru (Dist) - 560055.

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