1. FORMULATION AND EVALUATION OF FAST DISSOLVING FILM OF
LISINOPRIL
Synopsis
Submitted to
H.N.B. Garhwal (Central) University, Srinagar (Uttarakhand)
For The Award of Degree of
Master of Pharmacy
(Pharmaceutics)
By
SAURABH CHANDRA MISHRA
DEPARTMENT OF PHARMACEUTICAL SCIENCES
H.N.B. Garhwal (Central) University
Srinagar (Uttarakhand)
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2. DEPARTMENT OF PHATRMACEUTICAL SCIENCES
H.N.B Garhwal University, Chauras Campus-249161
Phone No: 01370-267395,FAX: 01346-252174,252247
Ref.no.pharm./14......
Date:
SYNOPSIS
Title:FORMULATION AND EVALUATION OF FAST DISSOLVING FILMS OF LISINOPRIL
Name of
Candidate : Saurabh Chandra Mishra
Enrollment Number: G1214506
Project Work: M.pharm (Pharmaceutics)2rd Year
H.N.B Garhwal (central) University
Srinagar(Uttarakhand)
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3. TITLE OF THE TOPIC:
“FORMULATION AND EVALUATION OF FAST DISSOLVING
FILMS OF LISINOPRIL”
BRIEF RESUME OF THE INTENDED WORK
Introduction :
Recently, fast dissolving drug delivery systems have started gaining popularity and acceptance as new
drug delivery systems, because they are easy to administer and lead to better patient compliance.
These delivery systems either dissolve or disintegrate in the mouth rapidly, without requiring any
water to aid in swallowing.1They also impart unique product differentiation, thus enabling use as line
extensions for existing commercial products. This novel drug delivery system can also be beneficial for
meeting the current needs of the industry are improved solubility/stability, biological half-life and
bioavailability enhancement of drugs.2,3.Although oral disintegrating tablets have an advantage of
administration without choking and fast disintegration; the disintegrated materials contained in them
are insoluble and remain until swallowing. In such cases formulation of fast dissolving film will be
advantageous.4,5
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4. Hypertension, commonly known as “High Blood Pressure”. Hypertension or High Blood Pressure is
a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated.Blood
pressure is a measurement of the force against the walls of your arteries as the heart pumps blood
through the body. High blood pressure increases chances of having a stroke, heart attack, heart
failure, kidney disease & early death. Commonly used prescription drugs include ACE inhibitors, alphablockers, angiotensin –ІІ receptor antagonists, beta-blockers, calcium channel blockers, diuretics
etc.6Hence in the present work, an attempt will be made to prepare and evaluate oral fast dissolving
film of Lisinopril for the effective management of hypertension and cardiac diseases.
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.
Pokharkar V et al (2007-08). Mouth dissolving tablets of Carvedilol were prepared with the
purpose of delivering the drug directly into the systemic circulation and by passing the hepatic first
pass metabolism with a concomitant increase in bioavailability, . The solubility of Carvedilol was
improved by forming inclusion complex with cyclodextrin which was then further used for the
formulation of mouth dissolving tablet. Differential scanning calorimetry and Infrared spectroscopy
results indicated no incompatibilities between drug-excipient mixtures. Effect of three different
superdisintegrants on disintegration was studied. The formulations were evaluated for drug
content,content uniformity, friability,disintegration time and in vitro dissolution. Tablets containing
Carvedilol-beta-cyclodextrin complex exhibited good tablet properties, with 90% drug dissolved
within 5 min. This demonstrated the effectiveness of using various superdisintegrants and
Carvedilol-beta-cyclodextrin complex in formulation of mouth dissolving tablet. 8
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5. Aditya Dinge and Mangal Nagarsenker (2008). Triclosan (TC) containing fast dissolving films for
local delivery to oral cavity was investigated by Various film forming agents, film modifiers and
polyhydric alcohols were evaluated for optimizing the composition of fast dissolving films. The
potential of poloxamer 407 and hydroxypropyl-β- cyclodextrin (HPBCD) to improve solubility of TC
was investigated. Fast dissolving films containing hydroxypropyl methylcellulose (HPMC), xanthan
gum, and xylitol were formulated. Use of poloxamer 407 and HPBCD resulted in significant
improvement in the solubility of TC. Fast dissolving films containing TC-HPBCD complex and TCPoloxamer 407 were formulated and evaluated for the in vitro dissolution profile and in vitro
microbiological assay. Films containing TC-Poloxamer 407 exhibited better in vitro dissolution
profile and in vitro antimicrobial activity as compared to the films containing TC-HPBCD complex.
Effect of incorporation of eugenol on the in vivo performance of TC-Poloxamer 407 containing films
was evaluated in human volunteers. Eugenol containing films improved the acceptability of TCPoloxamer 407 films with respect to taste masking and mouth freshening without compromising
the in vivo dissolution time.
KUNTE SAND TANDLE P (2010)Fast
dissolving films containing Verapamil were prepared and investigated.
The fast dissolving strips were prepared by solvent casting technique with the help of HPMC E6 and
maltodextrin. The strips were evaluated for drug content uniformity, film thickness, folding endurance,
in vitro disintegration time, in vitro dissolution studies, surface pH study, and palatability study.
Disintegration time showed by formulations was found to be in range of 20.4–28.6 sec. Based on the
evaluation parameters, the formulation containing 2% HPMC E6 and 3.5% maltodextrin showed
optimum performance against other formulations. It was concluded that the fast dissolving strips of
verapamil can be made by solvent casting technique with enhanced dissolution rate, taste masking,
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6. and hence better patient compliance and effective therapy.10
Semalty Aet al (2010)..Formulate and evaluate mucoadhesive drug delivery system of enalapril
maleate . The buccal films were prepared by solvent casting technique. Sodium carboxy methyl
cellulose, hydroxyl propyl methyl cellulose, hydroxylethyl cellulose and polyvinyl pyrrolidone K-90
were used as mucoadhesive polymers. Prepared films were evaluated for their weight, thickness,
surface pH, swelling index, drug content uniformity, in vitro residence time, folding endurance in vitro
release and permeation studies. It was found that the films containing 20 mg of enalapril maleate in
sodium carboxymethylcellulose 2% w/v and hydroxyl ethyl cellulose 2% w/v (formulation F5), showed
good swelling, a convenient residence time and promising controlled drug release as all the films
exhibited controlled release over more than 10 h in permeation studies. It was concluded that the
drug can be selected for the development of buccal film for effective therapeutic use.
. Fast dissolving films of levocetrizine were prepared by solvent casting method using different grades
of methocel K3, E3, E5, and E15 as film former and PG, PEG 400 and tween 80 as plasticizer. Bitterness
of levocetirizine was masked by forming inclusion complex with HP-ßCD. The complex was evaluated
by XRD, DSC and FT-IR. Optimized films were evaluated for mechanical properties, drug content and
dissolution characteristics. The combination of methocel E15 and PEG 400 exhibited excellent
mechanical properties, uniformity in drug content and in-vitro dissolution characteristics5
drug profile
Lisinopril dihydrate
Nomenclature:
INN: Lisinopril dihydrate
Chemical name: (2S) - 1- [(2S)-6-amino -2- [ [ (1S) – 1 – carboxy – 3 -
phenylpropyl] amino] hexanoyl] pyrrole – 2 - carboxylic acid
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7. Structure:
Molecular formula: C21H31N3O5,2H2O
Molecular weight: 441.5
Physical form: White to off white powder
Solubility: Lisinopril dihydrate is soluble in water, sparingly soluble in
methanol, and practically insoluble in acetone and in ethanol
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8. Need for the study:
Lisinopril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme.
Lisinopril is used to treat high blood pressure (hypertension), congestive heart failure, and to improve
survival after a heart attack. Lisinopril may also be used for purposes other than those listed in this
medication guide.
Lisinopril is a drug of the angiotensin converting enzyme (ACE) inhibitor class that is primarily used in
treatment of hypertension, congestive heart failure, heart attacks and also in preventing renal and
retinal complications of diabetes. Onset of action is 1-2 hours. Duration of action is found to be 24
hours (once daily dosing).Absorption of the drug is found to be absorbed slowly and incompletely from
GI tract(oral) and peak plasmaconcentration is achieved after 7 hours.The drug distribution i.e; protein
binding is not significantly bound i.e., is up to 25%.The excretion of the drug is via urine in unchanged
form of drug, and the elimination half-life of the drug is found to be 12 hours. The drug is given orally
in case of hypertension. Adult dose is initially 5-10 mg daily given at bedtime to avoid precipitous fall in
B.P. Patient with renovascular hypertension, volume depletion, severe hypertension; Initially 2.5-5 mg
once daily. Diuretic patients are given 5 mg once daily. Maintenance of the dose i.e. 20 mg once daily
up to 80 mg daily may be used if required.In case of children ≥6 years: initially up to 0.07 mg/kg( up to
5 mg once daily) can be given and adjusted the dose until desired B.P. is achieved. Bioavailability of the
drug is approximately 25%, but wide range of 6-60% is also reported. 7
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9. SALIENT FEATURES OF FAST DISSOLVING DRUG DELIVERY SYSTEM
1. Ease to administration for patients who are mentally ill, disabled and uncooperative.
2. Requires no water.
3. quick disintegration and dissolution of the dosage form.
4. Overcomes unacceptable taste of the drugs.
5. Can be designed to leave minimal or no residue in the mouth after administration and also to
provide a pleasant mouth feel.
6. Allows high drug loading.
7. Ability to provide advantages of liquid medication in the form of solid preparation.
8. Adaptable and ameanable to existing processing and packaging machinery.
9. Cost- effective.
The formulation of poorly water soluble drug compounds for oral delivery now present one of
the greatest challenges to formulation scientist in pharmaceutical industry.
The poor aqueous solubility of the drug result in variable dissolution profile hence poor
bioavailability. The solubility behavior of a drug is the key determination of its oral bioavailability.
Plan of work:
Fast dissolving films of Lisinopril will be prepared to provide fast action in hypertension with the
following objectives :9
1. To formulate Lisinopril fast dissolving films by using natural and synthetic polymers, following

10. MATERIALS & METHODS:
Source of Data :
 Primary literature: Journal publications
 Secondary literature: Abstracts (International Pharmaceutical Abstracts), online
material.
 Tertiary literature: Text Books.
 Prior unpublished research from our and other laboratories.
 Data will be obtained from Science Direct, and other internet facilities,
literature search and related articles from library of Shree Devi College of
Pharmacy, Digital Library of RGUHS, Bangalore, etc.
Journals
 Asian Journal of Pharmaceutics
 Journal of young Pharmacists
 Indian Journal of Pharmaceutical Science
 International Journal of Pharmacy and Pharmaceutical Science
 Journal of Pharmacy Research
 Digest Journal of Nano-materials & Bio-structures
 Research Journal of Pharmaceutical, Biological & Chemical sciences
 Journal of Liquid chromatography & related technologies
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11. Text Books and Pharmacopoeia
 Beckett AH, Stenlake JB, Practical Pharmaceutical Chemistry. 4 th ed.
 Delhi: CBS Publisher and Distributors, 1997
 Sethi PD, Quantitative Analysis of Drugs in Pharmaceutical Formulation,
 3rded. Delhi: CBS Publisher and Distributors
 Higuchi T And Brochman E, Hanseen H, Pharmaceutical Analysis, Delhi: CBS Publisher and
Distributors, 2005
 Mendham J, Denney RC, Barnes JD, K Thomas MJ, Vogel’s text Book of Quantitative Chemical
Analysis, 6thed. Pearson education Pvt. Ltd, 2002
 The Indian Pharmacopoeia, Government of India, Ministry of Health and Family Welfare,
Published by The Indian Pharmacopoeia commission Gaziabad, Volume 2 & 3, 2007
Internet Browsing
 www.sciencedirect.com
 www.google.com
 www.rxlist.com
 www.rjptonline.org
 www.jyoungpharm.in
 www.pharmainfo.net
 www.scipharm.at
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12.  www.jocpr.com
Methods of collection of data (including sampling procedures if any) :
The data related to the physicochemical properties of the drug will be collected from the drug
information center, various standard books, journals and other sources like research literature data
bases such science direct etc. and laboratory equipments.
• Attempts will be made to design fast dissolving films of Lisinopril with different polymers.
• Prepared fast dissolving films will be evaluated for
1.
Physical properties.
2.
Drug content.
3.
In vitro drug release and studying their release kinetics.
4.
In vivo studies for Pharmacodynamics parameters in detail.
REFERENCES :
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3 Mashru C, Sutariya V, Sankalia M, ParikhP. Development and evaluation of fast-dissolving film
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4 Nishimura M, Matsuura K, Tsukioka T, Yamashita H, Inagaki N, Sugiyama T, et al. In vitro and in
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13. vivo characteristics of prochlorperazine oral disintegrating film. Int J Pharm 2009; 368:98–102.
5 Shimoda
H, Taniguchi
K, Nishimura
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Preparation of a fast dissolving oral thin film containing dexamethasone: A possible application
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6 Available from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001502 [Last accessed on
2012 June 12].
7 The American Society of Health-System
Pharmacistshttp://www.drugs.com/monograph/lisinopril.html. Retrieved 3 April 2011.
8 Pokharkar V, Dhar S, Mandpe L. Studies on formulation development of mouth dissolving
tablets of Carvedilol. Hindustan Antibiot Bull 2007 -2008; 49-50(1-4):21-8.
9 Dinge A and Nagarsenker M. Formulation and Evaluation of Fast Dissolving Films for Delivery of
Triclosan to the Oral Cavity. AAPS Pharm SciTech 2008; 9(2): 349–56.
10 Kunte S and Tandale P. Formulation and Evaluation of fast dissolving films of verapamil J
PharmBioallied Sci2010; 2(4): 325–8.
11 Semalty A, Semalty M, Nautiyal U. Formulation and evaluation of mucoadhesive buccal films of
enalapril maleate. Indian J Pharm Sci 2010; 72(5):571-5.
12 SA Tayel, Soliman, II and D Louis. Formulation of ketotifenfumarate fast melt granulation
sublingual tablet. AAPS Pharm Sci Tech 2010; 11(2): 679-85.
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14 Yehia SA, El-Gazayerly ON, Basalious EB. Fluconazole mucoadhesive buccal films: In vitro/in
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